CN114395821B - Preparation method of conductive medicine-carrying composite fiber - Google Patents
Preparation method of conductive medicine-carrying composite fiber Download PDFInfo
- Publication number
- CN114395821B CN114395821B CN202210066131.4A CN202210066131A CN114395821B CN 114395821 B CN114395821 B CN 114395821B CN 202210066131 A CN202210066131 A CN 202210066131A CN 114395821 B CN114395821 B CN 114395821B
- Authority
- CN
- China
- Prior art keywords
- solution
- fiber
- aap
- pvp
- pedot
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000835 fiber Substances 0.000 title claims abstract description 284
- 239000002131 composite material Substances 0.000 title claims abstract description 157
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 114
- 229940079593 drug Drugs 0.000 claims abstract description 92
- 229920001609 Poly(3,4-ethylenedioxythiophene) Polymers 0.000 claims abstract description 73
- 238000009987 spinning Methods 0.000 claims abstract description 55
- 229920000144 PEDOT:PSS Polymers 0.000 claims abstract description 17
- 239000012792 core layer Substances 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 4
- 108010007100 Pulmonary Surfactant-Associated Protein A Proteins 0.000 claims description 89
- 102100027773 Pulmonary surfactant-associated protein A2 Human genes 0.000 claims description 89
- 230000001186 cumulative effect Effects 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 15
- 238000000338 in vitro Methods 0.000 claims description 12
- 238000013519 translation Methods 0.000 claims description 11
- 239000010410 layer Substances 0.000 claims description 9
- 230000009471 action Effects 0.000 claims description 8
- 230000002596 correlated effect Effects 0.000 claims description 8
- 230000008859 change Effects 0.000 claims description 7
- 230000001276 controlling effect Effects 0.000 claims description 7
- 239000011258 core-shell material Substances 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 3
- 238000005507 spraying Methods 0.000 claims description 3
- 230000000638 stimulation Effects 0.000 abstract description 18
- 230000005684 electric field Effects 0.000 abstract description 8
- 238000004132 cross linking Methods 0.000 abstract description 7
- 238000001723 curing Methods 0.000 abstract description 5
- 238000005516 engineering process Methods 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 84
- 239000008186 active pharmaceutical agent Substances 0.000 description 70
- 229920001940 conductive polymer Polymers 0.000 description 26
- 230000001965 increasing effect Effects 0.000 description 24
- 230000000694 effects Effects 0.000 description 10
- 239000012530 fluid Substances 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 238000013270 controlled release Methods 0.000 description 8
- 239000012528 membrane Substances 0.000 description 8
- 230000004044 response Effects 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 238000002441 X-ray diffraction Methods 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 238000002329 infrared spectrum Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000000465 moulding Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000000129 anionic group Chemical group 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000001000 micrograph Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000006479 redox reaction Methods 0.000 description 3
- 238000001878 scanning electron micrograph Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 238000004833 X-ray photoelectron spectroscopy Methods 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- DIOIOSKKIYDRIQ-UHFFFAOYSA-N ciprofloxacin hydrochloride Chemical compound Cl.C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 DIOIOSKKIYDRIQ-UHFFFAOYSA-N 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000013401 experimental design Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- -1 polytetrafluoroethylene Polymers 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 238000002166 wet spinning Methods 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 229910006069 SO3H Inorganic materials 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 238000000026 X-ray photoelectron spectrum Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 229940088516 cipro Drugs 0.000 description 1
- 229960001229 ciprofloxacin hydrochloride Drugs 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- ZOMNIUBKTOKEHS-UHFFFAOYSA-L dimercury dichloride Chemical class Cl[Hg][Hg]Cl ZOMNIUBKTOKEHS-UHFFFAOYSA-L 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920000128 polypyrrole Polymers 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
- D01F8/04—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers
- D01F8/10—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers with at least one other macromolecular compound obtained by reactions only involving carbon-to-carbon unsaturated bonds as constituent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/0007—Electro-spinning
- D01D5/0015—Electro-spinning characterised by the initial state of the material
- D01D5/003—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/0007—Electro-spinning
- D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/0007—Electro-spinning
- D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
- D01D5/0069—Electro-spinning characterised by the electro-spinning apparatus characterised by the spinning section, e.g. capillary tube, protrusion or pin
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/0007—Electro-spinning
- D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
- D01D5/0076—Electro-spinning characterised by the electro-spinning apparatus characterised by the collecting device, e.g. drum, wheel, endless belt, plate or grid
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F1/00—General methods for the manufacture of artificial filaments or the like
- D01F1/02—Addition of substances to the spinning solution or to the melt
- D01F1/09—Addition of substances to the spinning solution or to the melt for making electroconductive or anti-static filaments
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
- D01F8/18—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from other substances
Landscapes
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Textile Engineering (AREA)
- Mechanical Engineering (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Manufacturing & Machinery (AREA)
- Inorganic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Toxicology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method of a conductive drug-loaded composite fiber, which comprises the following steps: s1, PVP and SA are taken, water is added into the PVP and the SA respectively, and then the mixture is stirred and heated to obtain PVP solution and SA solution; s2, mixing PVP solution and SA solution, and then adding APP to form PVP/SA/AAP solution; s3, adding PEDOT into the PVP/SA/AAP solution: aqueous PSS solution forming PVP/SA/AAP/PEDOT: PSS mixed spinning solution; s4, taking the mixed spinning solution as a core layer and CaCl 2 The solution is sheath flow laminar flow, and the continuous conductive medicine carrying composite fiber is prepared by a coaxial microfluid spinning mode. The conductive medicine carrying fiber is prepared by utilizing an ionic crosslinking curing method and a coaxial microfluid spinning technology, so that the prepared conductive medicine carrying fiber has the corresponding capacity of an electric field, and the AAP controllable release of the conductive medicine carrying fiber is realized under the stimulation of voltage.
Description
Technical Field
The invention relates to a conductive medicine-carrying composite fiber, in particular to a preparation method of the conductive medicine-carrying composite fiber.
Background
The drug controlled release system is characterized in that certain intelligent high polymer materials are used as carriers of drugs to form a drug carrying system, so that the directional release can be realized, the release rate of the drugs can be controlled, the curative effect of the drugs can be fully exerted, the bioavailability of the drugs can be further improved, and the toxic and side effects of the high-concentration drugs can be reduced. The intelligent drug controlled release system which can respond to some external stimulus and is studied at present comprises pH response, temperature response, electric field response, magnetic field response and the like. Wherein an electrically responsive biomaterial is generally characterized by a rapid response compared to other types of stimuli-responsive. Meanwhile, the electric field response type drug controlled release system can be controlled by simple and portable equipment, and the electric field response type drug controlled release system is combined with a sensor or microchip, so that in-vitro drug release control and information feedback can be realized.
Electric field responsive drug controlled release systems typically achieve controlled release of the drug by electrochemical means. The drug carrier material changes upon stimulation by an electrical signal, thereby releasing the drug. The prior art has prepared by wet spinning techniques a polymer containing the conductive polymer PEDOT: the PSS hybridized fiber, the chitosan solution is coagulation bath, and then polypyrrole Ppy doped with ciprofloxacin hydrochloride Cipro is polymerized on the outer layer of the fiber by utilizing the electropolymerization technology, so as to prepare the coaxial conductive polymer fiber loaded with antibiotic medicine. The coagulation bath required for such wet spinning is generally a toxic liquid, is harmful to the body, requires post-removal, and may also destroy the activity of the drug molecules.
Therefore, it is necessary to study a conductive drug-loaded composite fiber and a preparation method thereof to solve the above-mentioned disadvantages of the preparation method.
Disclosure of Invention
The invention overcomes the defects of the prior art and provides a preparation method of a conductive medicine-carrying composite fiber.
In order to achieve the above purpose, the invention adopts the following technical scheme: the preparation method of the conductive drug-loaded composite fiber is characterized by comprising the following steps:
s1, PVP and SA are taken, water is added into the PVP and the SA respectively, and then the mixture is stirred and heated to obtain PVP solution and SA solution;
s2, mixing PVP solution and SA solution, and then adding APP to form PVP/SA/AAP solution;
s3, adding PEDOT into the PVP/SA/AAP solution: aqueous PSS solution forming PVP/SA/AAP/PEDOT: PSS mixed spinning solution;
s4, preparing continuous conductive drug-loaded composite fibers, namely PSAP composite fibers, in a microfluid spinning mode.
In a preferred embodiment of the present invention, the concentration of the PVP solution is 5 to 15wt%, the concentration of the SA solution is 1 to 2wt%, and the PVP solution and the SA solution are mixed according to a ratio of 1:1 to 2.
In a preferred embodiment of the present invention, the solution mass of the PEDOT is 30-50wt% to the PVP/SA/AAP solution: PSS.
In a preferred embodiment of the present invention, AAP is added to the PVP/SA/AAP solution in an amount of 0 to 30wt% based on the total solute.
In a preferred embodiment of the present invention, in the step S4, PVP/SA/AAP/PEDOT: PSS mixed spinning solution is used as a core layer and CaCl is used as a core layer 2 The solution was sheath flow laminar, PVP/SA/AAP/PEDOT: PSS mixed spinning solution and CaCl 2 Coaxially spraying out the fiber from the solution at different flow rates, and continuously rotationally drafting the fiber under the action of the rotational traction force of the fiber receiving device to obtain continuous fiber; and preparing the conductive medicine carrying composite fiber by setting the translation rate and the circulation times of the fiber receiving device.
In a preferred embodiment of the invention, the rotation speed of the fiber receiving device is 30-50 r/min, the translation speed of the fiber receiving device is 3-5 mm/min, the fiber receiving device is circularly translated once, the flow rate of the core layer solution is 16-28 mL/h, and the flow rate of the sheath flow layer solution is 8-14 mL/h.
The conductive drug-loaded composite fiber is prepared by the preparation method of the conductive drug-loaded composite fiber, and is characterized in that:
the conductive drug-carrying composite fiber is core-shell fiber, and AAP is uniformly dispersed in the conductive drug-carrying composite fiber in an amorphous state; the conductive drug-loaded composite fiber can realize the change of an electric signal by regulating and controlling the voltage so as to stimulate and control the in-vitro release amount of AAP.
In a preferred embodiment of the present invention, the conductive drug-loaded composite fiber has PEDOT: the PSS content is positively correlated with resistivity and cumulative AAP release percentage.
In a preferred embodiment of the invention, the same concentration of PEDOT: under the conductive drug-loaded composite fiber of the PSS, the cumulative release AAP percentage of the conductive drug-loaded composite fiber is positively correlated with the voltage.
In a preferred embodiment of the present invention, the conductive drug-loaded composite fiber includes PEDOT: the content of PSS is positively correlated with the breaking strength and negatively correlated with the elongation at break.
The invention solves the defects existing in the background technology, and has the following beneficial effects:
(1) The invention provides a preparation method of a conductive drug-loaded composite fiber, which comprises the steps of adding a conductive polymer PEDOT into PVP/SA/AAP mixed solution: PSS is prepared into conductive drug-carrying fibers by utilizing an ionic crosslinking curing method and a coaxial microfluid spinning technology, so that the prepared conductive drug-carrying fibers have the corresponding capacity of an electric field, and AAP (active pharmaceutical ingredient) controllable release of the conductive drug-carrying fibers is realized under the stimulation of voltage.
(2) By controlling PVP or AAP or conductive polymer PEDOT in the invention: PSS content, realizing control of the change of the cumulative release percentage of the conductive drug-loaded composite fiber; under the stimulation of voltage, the cumulative release percentage of the conductive drug-loaded composite fiber increases along with the increase of the voltage, and the controllable release of the drug can be realized by controlling the existence of an electric field and the magnitude of the voltage.
(3) The invention controls the output rate of the mixed spinning solution, the rotation rate of the fiber receiving device and the translation rate of the fiber receiving device, thereby controlling the conductive medicine carrying composite fiber to be formed into the fiber with regular arrangement and uniform diameter, and being beneficial to medicine release of the conductive medicine carrying composite fiber.
(4) The conductive drug-loaded composite fiber prepared by the invention is core-shell fiber, and has good compatibility with PEDOT: PSS by utilizing PVP, SA, AAP, thereby ensuring uniform mixing and improving the drug-loaded amount of the conductive drug-loaded fiber. In the drug release process, the conductive drug-loaded composite fiber controls two stages of swelling and degradation of the fiber skeleton by the presence or absence of voltage stimulation, thereby meeting the requirements of quick or slow release rate in different stages.
(5) The composite medicine carrying fiber prepared by utilizing the micro-fluid spinning has larger specific surface area, and meanwhile, the inside of the fiber is also provided with pores for storing medicines, so that the fiber can well encapsulate medicines after solidification, the Brownian movement of the medicines is also limited, the probability of mutual collision among medicine molecules is reduced, the formation of medicine crystal nucleus is avoided to a certain extent, and the medicine carrying capacity and the sustained-release effect of the conductive medicine carrying composite fiber are ensured.
(6) The composite medicine carrying fiber prepared by utilizing the micro-fluid spinning does not need to use high temperature, does not decompose or destroy activity on a carrier material or medicine, does not need to use high-voltage spinning, and does not generate toxic liquid in the process of preparing spinning solution.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required to be used in the embodiments or the description of the prior art will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments described in the present invention, and other drawings can be obtained according to these drawings without inventive effort for a person skilled in the art;
FIG. 1 is a flow chart of the preparation of a composite drug-carrying fiber based on micro-spinning of the present invention;
fig. 2 is a physical view of a PSAP composite fiber in accordance with a first embodiment of the invention;
fig. 3 shows a different PEDOT in a first embodiment of the invention: PEDOT: PSAP composite fiber SEM image of PSS content;
fig. 4 shows a different PEDOT in a first embodiment of the invention: scanning electron microscope images of PSAP composite fiber sections with PSS content;
fig. 5 is PVP, SA, AAP, PEDOT in embodiment three of the present invention: infrared spectrogram of PSS and PSAP composite fiber;
fig. 6 is an X-ray photoelectron spectrum of a PSAP composite fiber in a third embodiment of the invention;
fig. 7 is an X-ray diffraction diagram of a PSAP composite fiber in a third embodiment of the invention;
fig. 8 is a bar graph of breaking strength of PSAP composite fiber in a third embodiment of the invention;
fig. 9 is a standard curve and standard curve equation for AAP in phosphate buffered saline at ph=7.4 in example four of the present invention;
fig. 10 is a schematic diagram of an in vitro AAP release process from PSAP composite fibers in accordance with an embodiment of the invention;
fig. 11 is an in vitro release profile of AAP in a conductive drug-loaded PSAP conjugate fiber in accordance with example four of the present invention;
fig. 12 is a graph of CV cycles for a PSAP composite fiber in accordance with embodiment four of the invention;
fig. 13 is an SEM image of PSAP conjugate fiber before and after drug delivery in example four of the invention.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
As shown in fig. 1, a preparation flow chart of the composite drug-loaded fiber based on micro-fluid spinning is shown. The preparation method of the composite drug-loaded fiber based on micro-fluid spinning comprises the following steps:
s1, PVP and SA are taken, water is added into the PVP and the SA respectively, and then the mixture is stirred and heated to obtain PVP solution and SA solution;
s2, mixing PVP solution and SA solution, and then adding APP to form PVP/SA/AAP solution;
s3, adding PEDOT into the PVP/SA/AAP solution: aqueous PSS solution forming PVP/SA/AAP/PEDOT: PSS mixed spinning solution;
s4, preparing continuous conductive drug-loaded composite fibers, namely PSAP composite fibers, by adopting a microfluid spinning mode
Example 1
In this embodiment, PSA composite drug-loaded fibers are taken as an example, and the molding influence of different spinning solution concentrations on PSA composite drug-loaded fibers is verified, so that PEDOT with different concentration contents is verified: PEDOT: PSS is used for morphology characterization of PSAP composite fiber molding.
The preparation method of the PSA composite drug-carrying fiber and the PSAP composite fiber are different in that whether PEDOT is added into the mixed spinning solution: PSS. Firstly, verifying solution concentration, proportion and relevant parameters of a microfluidic spinning process in the PSA composite drug-loaded fiber to find PVP/SA/AAP mixed spinning solution concentration capable of continuously preparing the fiber, and preparing PVP/SA/AAP/PEDOT with mass fractions of 30wt%,40wt% and 50wt% of PVP/SA/AAP solution into the mixed spinning solution: and performing morphology characterization on the PSS mixed spinning solution.
Since the micro-fluid spinning is carried out at normal temperature and normal pressure, the mixed spinning solution is not subjected to other external force except the thrust of the injection pump in the whole continuous spinning process, so that the concentration of the solution is important to spinning in order to ensure the normal running of the spinning process. In order to ensure that the fiber only swells and is not dissolved in the drug release process, the fiber is rapidly solidified by adopting an ionic crosslinking method, and proper SA and CaCl are found out 2 Concentration is also important. Therefore, in order to verify the molding influence of different spinning solution concentrations on PVP/SA/AAP composite drug-carrying fibers, the embodiment is provided.
The PVP solution and the SA solution have certain viscosity, and the viscosity of the solution can be increased along with the increase of the concentration. Because the flow channel of the mixed spinning solution is relatively thin and narrow, when the concentration of the solution is too high, the viscosity is too high, so that the blocking phenomenon is very easy to occur, but when the concentration of the solution is too low, the fiber is not easy to form, and the broken ends are easy to occur.
To enable spinning experiments, ensure that the fiber does not break during spinning, 5wt%, 10wt% and 15wt% PVP solutions, and 1wt% and 2wt% SA solutions were respectively provided, and according to 1:1 and 1:2 to obtain PVP/SA/AAP mixed spinning solutions with different concentrations, and experimental design samples are shown in table 1.
Table 1 experimental design samples
It was found by the above experiments that a 15wt% PVP solution was mixed with a 2wt% SA solution according to 1:2 as core layer solution and 0.1mol/L CaCl 2 The solution is used as sheath fluid layer solution, and the fiber can be continuously prepared through coaxial microfluid spinning, so that the fiber is basically free from breakage.
Thus, in this example a 15wt% PVP solution was combined with a 2wt% SA solution according to 1:2 and preparing PVP/SA/AAP/PEDOT accounting for 30wt%,40wt% and 50wt% of the mass of the PVP/SA/AAP solution into the mixed spinning solution: PSS mixed spinning solution as core layer solution and CaCl of 0.1mol/L 2 The solution is used as sheath solution, and PSAP composite fiber is prepared by using the coaxial microfluid spinning process parameters and the method for ion crosslinking and curing the fiber, as shown in figure 2. From fig. 2, it can be seen that the PSA fiber is well formed, which illustrates that the above-mentioned set process parameters of coaxial microfluidic spinning and the method of ion crosslinking curing the fiber are still suitable for preparing PSAP conductive drug-loaded composite fibers. PVP, SA and PEDOT were also shown: the PSS has good compatibility and is beneficial to fiber forming.
This example also tested PEDOT at different concentration levels: PEDOT: PSS affects morphology of PSAP composite fiber formation. As shown in fig. 3, shown as different PEDOT: PEDOT: PSAP composite fiber SEM pictures of PSS content, wherein FIGS. 3a, 3b and 3c show PEDOT at 30wt%,40wt% and 50wt%, respectively: PEDOT: PSAP composite fiber scanning electron microscope image of PSS.
Fixing conductive adhesive on an electronic microscope table, then taking a plurality of PSAP composite fibers to be adhered on the conductive adhesive, spraying gold for 90 seconds, and observing the surface morphology features of the fibers by adopting an R-8100 cold field scanning electron microscope. The test condition is a voltage of 3kV and a voltage of 10mA. And (3) brittle fracture of the composite fiber by liquid nitrogen, and observing the cross-sectional morphology characteristics of the fiber by adopting the same test method and test conditions.
As can be taken from fig. 3, the PSAP fiber forms well, the fiber surface shows a linear crack-like change, and as PEDOT: the increase in PSS content increases linear cracking of the fiber surface because of PEDOT: PSS is an electrostatic complex, PEDOT is insoluble in water, and it can be uniformly dispersed in water by electrostatic complexing with PSS, ca when curing fiber by ionic crosslinking 2+ The addition of (a) may break the coulomb force between the molecular chains of PEDOT and PSS, a slight phase separation state may occur during the fiber formation, the PEDOT may be partially adhered to PVP/SA, and linear cracks may occur on the fiber surface due to linear accumulation. With PEDOT: the PSS content is increased, the diameter of the PSAP composite fiber is not changed basically, and the diameter of the fiber is about 50 mu m.
Fig. 4 is a different PEDOT: scanning electron microscope images of PSAP composite fiber sections with PSS content. From the figure, it can be observed that the PSAP composite fiber is a core-shell fiber, with a shell outside the fiber, as with PEDOT: the increase of the PSS conductive polymer content hardly changes the thickness of the shell layer. But the interior of the fiber follows the PEDOT: the increase in PSS conductive polymer content increases the linear cracks inside the fiber and the width of the cracks increases as well, because as PEDOT: the amount of PEDOT adhered to PVP and SA increased with increasing PSS content, more linear stacks were formed and the width of cracks increased. Again, no significant cavities were present inside the fiber, indicating PVP, SA, AAP and PEDOT: the PSS has good compatibility and can be uniformly mixed. At the same time, the linear cracks and the tiny pore size in the fiber are also beneficial to the encapsulation and release of the medicine.
Example two
In the preparation method, the micro-fluid spinning process parameters have a certain influence on fiber forming. Therefore, this example was designed to investigate the effect of microfluidic spinning process parameters on fiber formation.
The microfluidic spinning machine mainly comprises two parts of a microfluidic injection pump and a fiber receiving platform. The first part of microfluidic injection pump is used for controlling the output speed and output quantity of the spinning solution and mainly comprises: a dual channel syringe pump, a syringe, a polytetrafluoroethylene tube and a coaxial needle. The second part of fiber receiving platform is used for receiving the fibers and mainly comprises a roller receiver, a rotary motor, a circulating stepping translation platform, a heater and a control panel. Wherein the two-channel injection pump can respectively and independently control two injectors, different propelling speeds are set, and all parts of the micro-fluid spinning device are connected by a polytetrafluoroethylene tube and a connector.
The roller receiver on the micro-fluid spinning machine can generate traction force through continuous rotation, so that on one hand, the spinning solution can be stretched into fiber shape, on the other hand, the fiber solidified through ionic crosslinking can be received, and the traction force is provided, so that the fiber becomes more ordered. The rotational speed of the drum receiver is determined by the rotational speed of the rotating motor, so the rotational speed of the rotating motor affects the diameter of the fibers.
When the rotating speed is too low, the receiver cannot rapidly draft out the fibers from the needle head, the fibers cannot be molded, and when the rotating speed is too high, the traction force provided by the receiver is too large, the fibers can be broken, and the number of broken fibers is relatively large. In order to obtain the fiber membranes which are orderly arranged and uniform in diameter, the device is beneficial to later drug release experiments, and the receiver can circularly move at a certain translation speed, so that the orderly and uniformly spaced fiber membranes can be collected on the roller. The translational speed and number of cycles of the receiver directly affect the size of the inter-fiber spacing and the density of the fiber membranes.
PVP/SA/AAP/PEDOT: the output speed of the PSS mixed spinning solution is controlled by the propelling speed of the injection pump, and proper flow rates of the core layer solution and the sheath flow layer solution are required to be found, so that the fiber with good molding and uniform arrangement can be obtained.
Thus, the micro-fluid spinning machine in this example was PVP/SA/AAP/PEDOT determined by syringe pump: the output rate of the PSS mixed dope, the rotation rate of the motor on the fiber receiving platform, and the cyclic step-by-step translational rate affect the diameter, spacing, and uniformity of the fibers. According to the embodiment, the composite fiber membrane which is orderly arranged, uniform in diameter and adjustable in size can be obtained through the optimized setting of the three process parameters. The experimental protocol of table 2 was designed according to the three process parameters described above.
Table 2 experimental protocol
As shown in Table 2, when the rotation speed of the drum receiver was 50r/min, the translation speed of the receiver was 4mm/min, the circulation translation was performed once, the flow rate of the core layer solution was 28mL/h, and the flow rate of the sheath layer solution was 14mL/h, a fiber having good formation was obtained, and the fiber was continuously produced.
According to the embodiment, when the rotation speed of the roller receiver is 50r/min, the translation speed of the receiver is 4mm/min, the circulating translation is carried out once, the flow rate of the core layer solution is 28mL/h, the flow rate of the sheath flow layer solution is 14mL/h, and the ratio of 15wt% PVP solution to 2wt% SA solution is 1:2 and configuring PVP/SA/AAP/PEDOT at mass fractions of 30wt%,40wt% and 50wt% of PVP/SA/AAP/PEDOT: the PSS mixed spinning solution is used as a core layer solution and 0.1mol/L calcium chloride solution is used as a sheath flow layer solution, and the fiber can be continuously prepared through coaxial microfluid spinning.
Example III
This example is characterized by morphology of PSAP composite fibers prepared in the previous examples.
(1) PSAP composite fiber Fourier infrared spectrum FITR test
Fig. 5 is PVP, SA, AAP, PEDOT: infrared spectra of PSS and PSAP composite fibers. Fig. 5a is PEDOT: infrared spectrum of PSS sample at 1186cm -1 A typical absorption peak of sulfonic acid groups in PSS was observed at 1632cm -1 And 1540cm -1 The absorption peaks of (a) are-c=c-in PEDOT and-C in thiophene, respectivelyStretching vibration of =c-. Fig. 5e is an infrared spectrum of a PSAP composite fiber from which PVP, SA, AAP and PEDOT can be observed: characteristic absorption peaks of PSS, no new characteristic peak appears, demonstrating PVP, SA, AAP and PEDOT: PSS is also physically combined, and hydrogen bonding exists among four substances.
(2) XPS analysis of PSAP composite fiber X-ray photoelectron spectroscopy
As shown in fig. 6, C, N and O elements are present in both PSA and PSAP composite fibers. With the conductive polymer PEDOT: the PSS is added, and the PSAP composite fiber shows an photoelectron characteristic peak belonging to the element S2p at 168 eV. Figures 6b, 6c and 6d are high resolution spectral diagrams of C, N and S elements, respectively, in a PSAP composite fiber. After peak splitting, the PSAP composite fiber has a characteristic peak of C-C (284.6 eV) in PVP, a characteristic peak of C-O (284.8 eV) in SA, a characteristic peak of C-N (285.7 eV) in PVP, a characteristic peak of C=O (286.4 eV) in PVP and AAP, and a characteristic peak of-COOH (288.6 eV) in SA, as shown in FIG. 6 b. In FIG. 6C, a characteristic peak of C-N (399.5 eV) belonging to PVP can be observed. In FIG. 6d, three photoelectron characteristic peaks of 164eV, 168eV and 169eV can be observed, which correspond to RS.SO3-, SO3H and SO 42-in PSS, respectively. After comparative analysis, no characteristic peak of new chemical bonds appears in the PSAP composite fiber, and only PVP, SA, AAP and PEDOT appear: the characteristic peaks of the PSS components, further illustrating PVP, SA, AAP and PEDOT: the lack of covalent bonds between PSS, hydrogen bonding and van der waals forces are the primary driving forces for the assembly of the fiber components, consistent with the results of infrared spectroscopy.
(3) PSAP composite fiber X-ray diffraction XRD analysis
To explore the conductive polymer PEDOT in PSAP composite fiber: whether PSS has an effect on the crystallization of model drug AAP, fig. 7 is AAP, PEDOT: XRD patterns of PSS, PSA composite fibre membranes and PSAP composite fibre membranes. Fig. 7a, 7b and 7c are AAP, PEDOT respectively: as can be seen from curve a, typical characteristic diffraction peaks appear at 12.04 °,13.76 °, 15.4 °, 16.66 °, 18.12 °, 20.3 °, 23.38 °, 24.32 °, 26.5 °, 29, 22 ° and 32.44 ° for AAP prodrugs. From curve b, PEDOT can be seen: PSS has little crystallinity. From curve c, it can be seen that no diffraction peak of AAP was seen in the PSA composite fiber, indicating that the PSA composite fiber can effectively inhibit crystallization of AAP. Curve d is the XRD pattern of the PSAP composite fiber film, showing diffraction peaks at 13.22 ° and 31.84 ° compared to curves a and c, due to the hydrophobic PEDOT: in contrast to PSS, both SA and PSS have a hydrophilic effect, in which-COO-and-SO 3-are easily bound to metal ions in solution, forming entangled composite structures that wrap around PEDOT, inducing PEDOT crystallization, SO that characteristic diffraction peaks appear on PSAP composite fibers. Typical characteristic diffraction peaks for AAP are not seen yet, indicating that PSAP composite fibers inhibit crystallization of AAP.
(4) PSAP composite fiber dimensional conductivity analysis
10 composite fibers with fixed length of 2cm are randomly extracted, the resistance of the fibers is measured by using a desk digital bridge, the cross-section SEM (scanning electron microscope) graph of the fibers is analyzed by using Image J software, the effective cross-sectional area of the fibers is calculated, and the conductivity of the fibers is calculated by using a formula.
The formula:where σ is the conductivity of the fiber, R is the electrical resistance of the fiber, S is the effective cross-sectional area of the fiber, and L is the fiber length.
Table 3 is a different PEDOT: PSAP composite fiber conductivity at PSS content from the table we can observe that with the conductive polymer PEDOT: the increase in PSS content, the conductivity of the fiber also increases, indicating that the conductivity of the fiber follows the PEDOT: the higher the PSS content, the better the conductivity of the fiber, and the more rapidly the fiber responds to electrical signals.
Table 3 different PEDOT: conductivity of PSAP composite fiber with PSS content
(5) PSAP composite fiber dimensional mechanical property analysis
The fiber is prepared according to the gauge length of 200mm, the breaking strength of the composite fiber is tested by using an Instron5967 material tester, each sample is tested for 30 times, and the drawing speed is 20mm/min, and the average value is taken as a test result.
Fig. 8 is a bar graph of breaking strength of PSAP composite fiber, from which it can be observed that the breaking strength of PS composite fiber without added model drug AAP is 37.27 ±4.17MPa, and that the breaking strength of PSA composite fiber after added AAP is 39.14 ±5.31MPa, along with the conductive polymer PEDOT: and adding PSS, increasing the breaking strength of the PSAP composite fiber to 50.17+/-6.06 MPa, and continuously increasing PEDOT: the PSS content, the breaking strength of the PSAP composite fiber is also increased, and 40wt% and 50wt% of PEDOT: PSAP composite fiber breaking strength of PSS is 53.58+ -7.11 MPa and 65.53+ -5.5 MPa respectively.
Fig. 8b is a stress strain plot of a PSAP composite fiber from which it can be observed that with the conductive polymer PEDOT: the PSS content is increased, the breaking strength of the PSAP composite fiber is increased, and the breaking elongation is reduced. This is because SA induces crystallization of part of PEDOT, the crystalline region of PSAP composite fiber increases, the amorphous region in the fiber decreases, and slip between macromolecular chains decreases, so that the breaking strength of the composite fiber increases and the breaking elongation decreases.
Example IV
This example measures the in vitro release of AAP from PSAP conjugate fibers prepared in the above examples.
Fig. 9 is a standard curve and standard curve equation for AAP in phosphate buffer at ph=7.4. The standard curve shows that AAP concentration is in the range of 0.5 μg/mL-50 μg/mL, and the absorbance and concentration show good linear relationship.
Fig. 10 is a schematic illustration of the in vitro AAP release process from PSAP conjugate fibers. And weighing the PSAP composite fiber membrane, wrapping the fiber membrane on a working electrode, fixing the upper end and the lower end of the working electrode by using a conductive adhesive tape, putting the working electrode and the saturated calomel electrode into PBS buffer solution together, and connecting the other end of the electrode with a direct current power supply. After sealing, a power supply is turned on to provide electric stimulation for the conductive medicine carrying fiber, and then slow release solutions are respectively taken at 2h,4h,6h,8h,10h,12h,24h,26h,28h,30h,32h,34h,36h,48h,50h,52h,54h,56h,58h,60h and 72h, and then diluted, and the slow release solutions are measured in the sameUltraviolet absorbance at 245nm, and adding equal amount of PBS buffer solution into the slow release system to keep the solution capacity constant, and taking three parallel samples of each drug-carrying fiber. And calculating the AAP content according to a standard curve equation of AAP, calculating the cumulative release percentage of AAP according to a formula, and drawing an in-vitro release curve of the conductive drug-loaded PSAP fiber. Wherein, the formula is: q is AAP cumulative release percentage, v is volume of slow-release solution PBS, v d For the volume of PBS after dilution c i Drug concentration (μg/mL) in the released liquid at the time of sampling for the ith exchange, A is AAP mass (μg) contained in the composite drug-carrying fiber, and n is the number of times of sampling.
Fig. 11 is an in vitro release profile of AAP in a conductive drug-loaded PSAP conjugate fiber. FIGS. 11a, 11b and 11c are in vitro graphs showing sustained stimulation of PSAP-30% (30 wt% PEDOT: PSS) composite fibers, PSAP-40% (40 wt% PEDOT: PSS) composite fibers and PSAP-50% (50 wt% PEDOT: PSS) composite fibers, respectively, at different voltages.
From the figure it is evident that in the conductive polymer PEDOT: at a constant PSS content, the cumulative percent release of PSAP composite fiber increases with increasing voltage. Figures 11d, 11e and 11f are in vitro drug release profiles of PSAP-30% composite fiber, PSAP-40% composite fiber and PSAP-50% composite fiber, respectively, stimulated continuously at the same voltage. It can be seen from the figure that at the same voltage, with the conductive polymer PEDOT: the cumulative percent release of PSAP composite fibers increases with increasing PSS content.
FIGS. 11g, 11h and 11i are graphs showing cumulative release profiles of in vitro drug release from PSAP-30% composite fiber, PSAP-40% composite fiber and PSAP-50% composite fiber, respectively, stimulated indirectly by different voltages. It can be seen from the figure that when the power is turned on, providing an electric field environment to the PSAP composite fiber, the fiber can rapidly respond to the electrical signal to release the drug. After the power is turned off and the voltage is removed, the PSAP composite fiber stimulated by the voltage still has a higher AAP release rate, which indicates that the microstructure change of the fiber after the electric stimulation is irreversible, so that the drug release can be continuously promoted. Therefore, the PSAP composite fiber can realize the controllable release of the drug by controlling the electric signal and the existence of the electric stimulation.
From tables 4, 5 and 6, it can be seen that 30wt%,40wt% and 50wt% pedot: PSS content, PSAP composite fiber with AAP content of 10% in the absence of electrical stimulation, cumulative release percentage for the first 12 hours was 48.86%, 51.32% and 55.36%, respectively; the cumulative release percentages for 72h were 57.99%, 60.31% and 62.62%, respectively. This is because with the conductive polymer PEDOT: the more and the wider the microcracks formed in the fiber and on the surface are, the more the release path of the drug is increased, the more the release amount of the drug is increased, so the cumulative release rate of the PSAP composite fiber is increased. Providing a voltage of 1V to the PSAP composite fiber, wherein the cumulative percent release of the PSAP-30% composite fiber, the PSAP-40% composite fiber and the PSAP-50% composite fiber over the first 12 hours are 56.86%, 58.26% and 60.46%, respectively; the cumulative release percentages for 72h were 67.08%, 69.29% and 71.56%, respectively. This is because with the conductive polymer PEDOT: the PSS content is increased, the conductivity of the PSAP composite fiber is improved, the sensitivity of the fiber to electric signals is improved under the same voltage, the influence of electric stimulation on the change of the microstructure inside the PSAP composite fiber is increased, so that the content of the conductive polymer is increased, and the cumulative release percentage of the composite fiber is also increased. The conductivity of the fiber is shown to have an effect on the drug release rate of the PSAP composite fiber. When the voltage was increased to 1.5v, the cumulative percent release of PSAP-30% composite fiber, PSAP-40% composite fiber and PSAP-50% composite fiber over the first 12 hours was 59.75%, 62.43% and 65.17%, respectively. The cumulative percent release of PSAP-40% and PSAP-50% composite fibers over the first 12 hours was increased by 2.89%, 4.17% and 4.71%, respectively, as compared to 1V voltage stimulation. It is explained that the change of the voltage has an effect on the drug release rate of the PSAP composite fiber. The cumulative release percentage after 72h was 69.4%, 72.29% and 74.74%, respectively, increased by 2.32%, 3% and 3.18% compared to the 1V voltage stimulus. The electric signal can be changed by regulating the voltage, so that the drug release amount can be controlled.
Table 4 30wt% pedot: AAP cumulative Release Rate in PSAP Complex fiber of PSS
Table 540 wt% pedot: AAP cumulative Release Rate in PSAP Complex fiber of PSS
Table 6 50wt% pedot: AAP cumulative Release Rate in PSAP Complex fiber of PSS
Drug release mechanisms of drug controlled release systems generally responsive to electrical stimulation and based on conductive polymers are classified into electrostatic actuation and deformation actuation. The electrostatic driving means that when negative voltage is applied to the conductive polymer, the oxidized conductive polymer is changed into a reduced state, the total amount of positive charges on the molecular chain of the conductive polymer is reduced, the electrostatic attraction between the medicine and the polymer in the system is reduced, and the small-volume anionic medicine is released from the polymer system; when a positive voltage is applied to the conductive polymer, the conductive polymer in a reduced state can undergo oxidation reaction, the electropositivity of the molecular skeleton of the conductive polymer is increased, and the cationic drug can migrate outwards under the action of electrostatic repulsion. The controlled release of drugs by such electrostatic action is known as electrostatically driven release. Deformation driving means that in the process of oxidation-reduction reaction of the conductive polymer, the length, volume, color and the like of the conductive polymer are changed along with the migration and the immigration of ions and solvents, the migration of pi electrons and the electrostatic repulsion between like charges, so that the microstructure in the system is changed, and the medicine can be released from the system.
Fig. 12 is a graph of CV cycles for PSAP composite fibers illustrating that the PSAP composite fibers may undergo redox reactions at a lower voltage. Fig. 12b is the zeta potential of AAP in PBS buffer ph=7.4, indicating that AAP is an anionic drug. The combination of the two proves that the drug release mechanism of the PSAP composite fiber is electrostatic drive. When negative voltage is applied to the PSAP composite fiber, oxidation-reduction reaction is carried out on the conductive polymer PEDOT in the fiber, the total amount of positive charges on the PEDOT molecular chain is reduced, the electrostatic attraction between the drug and the polymer in the fiber is reduced, and the anionic drug AAP is released from the polymer system.
Fig. 13 is an SEM image of PSAP conjugate fiber before and after drug release. Fig. 13a is a pre-release PSAP conjugate, 13b is a 72h post-release PSAP conjugate without electrical stimulation, and 13c is a 72h post-release PSAP conjugate at 1V voltage.
It can be seen from the figure that under the action of the voltage, the morphology of the fiber is greatly changed, the diameter of the fiber is thinned, and the surface is provided with rugged channels. Indicating that under the action of electric stimulation, the microscopic morphology of the fiber can be changed, the degradation rate of the fiber skeleton can be accelerated, the volume of the fiber can be changed, and the medicine can be released. And under the action of electric stimulation, the accumulated drug release percentage of the PSAP composite fiber is increased, which indicates that the deformation drive is also the drug release mechanism of the PSAP composite fiber.
Tables 7 and 8 are drug release kinetics model fits for the release profiles of PSAP-30% composite fiber without voltage stimulus and 1V voltage stimulus, respectively. According to the correlation coefficient R 2 The drug release kinetics model of the PSAP complex fiber was evaluated to be more consistent with the Weibull model and the Ritger-Peppas model. The explanation PSAP composite fiber drug release mechanism also comprises two processes of swelling and degradation of a fiber skeleton.
In conclusion, the release mechanism of the PSAP composite fiber and the PSA composite fiber is consistent under the condition of no electric stimulation. Under the action of electric stimulation, the drug release mechanism of the PSAP composite fiber is accompanied by electrostatic driving and deformation driving.
Table 7 model fitting of drug release kinetics for PSAP fiber release profile
Table 8 model fitting of drug release kinetics for PSAP fiber release profile
The above-described preferred embodiments according to the present invention are intended to suggest that, from the above description, various changes and modifications can be made by the person skilled in the art without departing from the scope of the technical idea of the present invention. The technical scope of the present invention is not limited to the description, but must be determined according to the scope of claims.
Claims (5)
1. The preparation method of the conductive drug-loaded composite fiber is characterized by comprising the following steps:
s1, PVP and SA are taken, water is added into the PVP and the SA respectively, and then the mixture is stirred and heated to obtain PVP solution and SA solution; the concentration of the PVP solution is 15wt% and the concentration of the SA solution is 2wt%;
s2, mixing PVP solution and SA solution in the S1 according to the following ratio of 1:2, adding AAP to form PVP/SA/AAP solution, wherein the addition amount of the AAP accounts for 0-30wt% of the total solute and is not 0wt%;
s3, adding PEDOT into the PVP/SA/AAP solution: aqueous PSS solution forming PVP/SA/AAP/PEDOT: PSS mixed spinning solution; wherein, the PVP/SA/AAP solution is provided with PEDOT with the mass percentage of 30-50 wt%: PSS;
s4, preparing continuous conductive drug-loaded composite fibers, namely PSAP composite fibers, in a microfluid spinning mode; wherein, PVP/SA/AAP/PEDOT: PSS mixed spinning solution is used as a core layer, and CaCl of 0.1mol/L is used as a core layer 2 The solution is sheath flow laminar flow, PVP/SA/AAP/PEDOT: PSS mixed spinning solution and CaCl 2 Coaxially spraying out the fiber from the solution at different flow rates, and continuously rotationally drafting the fiber under the action of the rotational traction force of the fiber receiving device to obtain continuous fiber; preparing and forming conductive drug-loaded composite fibers by setting the translation rate and the circulation times of the fiber receiving device; the rotating speed of the fiber receiving device is 50r/min, the translation speed of the fiber receiving device is 4mm/min, the fiber receiving device is circularly translated once, the flow rate of the core layer solution is 28mL/h, and the flow rate of the sheath flow layer solution is 14mL/h.
2. A conductive drug-loaded composite fiber prepared by the method for preparing the conductive drug-loaded composite fiber according to claim 1, which is characterized in that:
the conductive drug-carrying composite fiber is core-shell fiber, and AAP is uniformly dispersed in the conductive drug-carrying composite fiber in an amorphous state; the conductive drug-loaded composite fiber can realize the change of an electric signal by regulating and controlling the voltage so as to stimulate and control the in-vitro release amount of AAP.
3. The electrically conductive drug-loaded composite fiber of claim 2, wherein: at the same voltage, PEDOT in the conductive drug-loaded composite fiber: the PSS content is positively correlated with resistivity and cumulative AAP release percentage.
4. The electrically conductive drug-loaded composite fiber of claim 2, wherein: PEDOT at the same concentration: under the conductive drug-loaded composite fiber of the PSS, the cumulative release AAP percentage of the conductive drug-loaded composite fiber is positively correlated with the voltage.
5. The electrically conductive drug-loaded composite fiber of claim 2, wherein: PEDOT in the conductive drug-carrying composite fiber: the content of PSS is positively correlated with the breaking strength and negatively correlated with the elongation at break.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210066131.4A CN114395821B (en) | 2022-01-20 | 2022-01-20 | Preparation method of conductive medicine-carrying composite fiber |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210066131.4A CN114395821B (en) | 2022-01-20 | 2022-01-20 | Preparation method of conductive medicine-carrying composite fiber |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114395821A CN114395821A (en) | 2022-04-26 |
| CN114395821B true CN114395821B (en) | 2023-10-27 |
Family
ID=81232916
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210066131.4A Active CN114395821B (en) | 2022-01-20 | 2022-01-20 | Preparation method of conductive medicine-carrying composite fiber |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114395821B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2004202461A1 (en) * | 2000-01-28 | 2004-07-01 | Smithkline Beecham Corporation | Electrospun pharmaceutical compositions |
| CN102817105A (en) * | 2012-08-24 | 2012-12-12 | 上海交通大学 | Preparation method of core-shell structured synthetic polymer-natural polymer composite fiber |
| CN107740196A (en) * | 2017-10-12 | 2018-02-27 | 南京科技职业学院 | A kind of preparation method based on micro-fluidic doughnut |
| KR20200038374A (en) * | 2018-10-02 | 2020-04-13 | 연세대학교 산학협력단 | Micro-patterned conductive hydrogel hybrid system scaffold and preparing method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI777158B (en) * | 2019-09-23 | 2022-09-11 | 明志科技大學 | Method of producing electrically conductive polymers and removing protein-bound uremic toxins, conductive nanofiber mat, and bioelectronic interface denvice |
-
2022
- 2022-01-20 CN CN202210066131.4A patent/CN114395821B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2004202461A1 (en) * | 2000-01-28 | 2004-07-01 | Smithkline Beecham Corporation | Electrospun pharmaceutical compositions |
| CN102817105A (en) * | 2012-08-24 | 2012-12-12 | 上海交通大学 | Preparation method of core-shell structured synthetic polymer-natural polymer composite fiber |
| CN107740196A (en) * | 2017-10-12 | 2018-02-27 | 南京科技职业学院 | A kind of preparation method based on micro-fluidic doughnut |
| KR20200038374A (en) * | 2018-10-02 | 2020-04-13 | 연세대학교 산학협력단 | Micro-patterned conductive hydrogel hybrid system scaffold and preparing method thereof |
Non-Patent Citations (6)
| Title |
|---|
| Fiber Based Approaches as Medicine Delivery Systems;Farrokh Shari fi等;ACS Biomater. Sci. Eng(第2期);1411−1431 * |
| Multifunctional Micro/Nanoscale Fibers Based on Microfluidic Spinning Technology;Xiang-Yun Du等;Adv. Mater(第31期);1903733 * |
| 对乙酰氨基酚复合微囊缓释栓的制备及体外释放度研究;王磊等;中国医院药学杂志(第09期);19-23 * |
| 水杨酸对Na2CO3胁迫下铁皮石斛幼苗生理特性的影响;史俊等;江苏农业科学(第23期);184-188 * |
| 海藻酸钠-聚乙烯醇复合纤维的研制及性能表征;朱剑等;材料导报;494-498、501 * |
| 烯丙醇聚氧烷基醚的浊点及影响因子;薛震等;石油学报(第05期);104-107 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114395821A (en) | 2022-04-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Nadaf et al. | Recent update on electrospinning and electrospun nanofibers: current trends and their applications | |
| Chunder et al. | Fabrication of ultrathin polyelectrolyte fibers and their controlled release properties | |
| Bagheri et al. | Tissue engineering with electrospun electro-responsive chitosan-aniline oligomer/polyvinyl alcohol | |
| Abd Razak et al. | A review of electrospun conductive polyaniline based nanofiber composites and blends: processing features, applications, and future directions | |
| Ignatova et al. | Electrospinning of poly (vinyl pyrrolidone)–iodine complex and poly (ethylene oxide)/poly (vinyl pyrrolidone)–iodine complex–a prospective route to antimicrobial wound dressing materials | |
| CN1319637C (en) | Chitose microsphere and microcapsule with uniform size and its preparation method | |
| US20080290554A1 (en) | Oriented Polymer Fibers and Methods for Fabricating Thereof | |
| US20120040581A1 (en) | Template-supported method of forming patterns of nanofibers in the electrospinning process and uses of said nanofibers | |
| US20190343772A1 (en) | Nanofibrous mat containing ceramic particles with releasable dopant | |
| WO2008022993A2 (en) | Process for producing nano- and mesofibres by electrospinning colloidal dispersions | |
| WO2010106063A2 (en) | Composite materials loaded with therapeutic and diagnostic agents comprising polymer nanoparticles and polymer fibers | |
| Liu et al. | Preparation and characterization of electrospun conductive janus nanofibers with polyaniline | |
| CN114395821B (en) | Preparation method of conductive medicine-carrying composite fiber | |
| Baptista et al. | Electronic control of drug release from gauze or cellulose acetate fibres for dermal applications | |
| WO2008049397A2 (en) | Method for producing nano- and mesopolymer fibers by electrospinning polyelectrolytes of opposite charge | |
| Fang et al. | PEDOT: PSS‐Based Microfluidic‐Spun Microfibers for Tunable Release of Acetaminophen via Electrical Stimulation | |
| Jegina et al. | Evaluation of aloe vera extract loaded polyvinyl alcohol nanofiber webs obtained via needleless electrospinning | |
| CN114525598A (en) | Preparation method of conductive drug-loaded composite fiber | |
| Hamzah et al. | Tensile and wettability properties of electrospun polycaprolactone coated with pectin/polyaniline composite for drug delivery application | |
| Behbood et al. | Mucoadhesive electrospun nanofibers of chitosan/gelatin containing vancomycin as a delivery system | |
| CN114351287B (en) | Preparation method of composite drug-loaded fiber based on micro-fluid spinning | |
| Naseri et al. | Application of electrowetting on dielectric (EWOD) in drug release control and release-on-demand | |
| Wang et al. | Effect of experimental parameters on the formation of chitosan–poly (acrylic acid) nanofibrous scaffolds and evaluation of their potential application as DNA carrier | |
| Meghana et al. | Electrospinning Nanotechnology-A Robust Method for Preparation of Nanofibers for Medicinal and Pharmaceutical Application. | |
| Gospodinova et al. | Investigation of the effect of polymer solution electrospinning system parameters on the nanofibers morphology |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Lin Hong Inventor after: Fang Ying Inventor after: Chen Yuyue Inventor after: Zhang Desuo Inventor before: Chen Yuyue Inventor before: Fang Ying Inventor before: Lin Hong Inventor before: Zhang Desuo |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |