CN114712333B - Microfluidic biological barrier membrane for drug release - Google Patents
Microfluidic biological barrier membrane for drug release Download PDFInfo
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- CN114712333B CN114712333B CN202210380422.0A CN202210380422A CN114712333B CN 114712333 B CN114712333 B CN 114712333B CN 202210380422 A CN202210380422 A CN 202210380422A CN 114712333 B CN114712333 B CN 114712333B
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- 239000003814 drug Substances 0.000 title claims abstract description 343
- 229940079593 drug Drugs 0.000 title claims abstract description 192
- 239000012528 membrane Substances 0.000 title claims abstract description 110
- 230000004888 barrier function Effects 0.000 title claims abstract description 73
- 238000003860 storage Methods 0.000 claims abstract description 58
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- 229940124350 antibacterial drug Drugs 0.000 abstract description 2
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- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 description 9
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Classifications
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- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02W—CLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO WASTEWATER TREATMENT OR WASTE MANAGEMENT
- Y02W90/00—Enabling technologies or technologies with a potential or indirect contribution to greenhouse gas [GHG] emissions mitigation
- Y02W90/10—Bio-packaging, e.g. packing containers made from renewable resources or bio-plastics
Abstract
The invention relates to a microfluidic biological barrier membrane for drug release, which has a three-layer structure, namely a drug release layer, a middle connecting layer and a non-drug release bottom layer. The medicine release layer is provided with a medicine inlet, a medicine release outlet and a positioning hole; the middle connecting layer is provided with a positioning hole, two symmetrical and unconnected medicine storage tanks are arranged at the middle part of the middle connecting layer, and a medicine inlet channel and a medicine release outlet channel which are communicated with the medicine storage tanks are arranged; the non-drug release bottom layer is only provided with positioning holes; the three-layer structure is bonded together through the positioning holes of each layer, and the upper side and the lower side of the middle connecting layer are respectively attached to the drug release layer and the non-drug release bottom layer. Because the medicine solution and the medicine carrying nano-microsphere exist in the medicine storage pool at the same time, the medicine carrying microsphere can supplement medicine quantity for the medicine storage pool in the medicine release process, and the effective medicine concentration is maintained. The micro-fluidic biological barrier membrane can continuously and slowly release the antibacterial drugs for 5 days, and the release rate of the drugs is controlled.
Description
Technical Field
The invention relates to the technical field of microfluidics, in particular to a microfluidic biological barrier membrane for drug release.
Background
Periodontal bone tissue defects caused by periodontitis and peri-implant inflammation are a great challenge in oral clinic, and are important research points in the related fields, especially in the field of oral implantation. Guided bone tissue regeneration (guided bone regeneration, GBR) membranes are biological barrier membranes placed at bone defects, GBR biological barrier membranes play an important role in guided tissue regeneration. It can be used as a barrier in periodontal surgery to prevent gingival epithelium from growing along root surface during healing, and guide periodontal ligament cells with new adhesion ability to preferentially occupy root surface to form new adhesion healing. However, biological barrier membranes widely used at present mainly rely on the growth potential of organisms to repair defects, and can not effectively prevent complications such as postoperative infection.
One of the major complications in conducting bone tissue regeneration surgery using GBR biological barrier membranes is postoperative infection. An effective method of treating infections is to thoroughly clear the affected area and to apply antibiotic adjuvant therapy topically. Compared with the whole body, the local administration has lower side effect on the body and reduces the occurrence probability of organ damage. Therefore, researchers develop drug-carrying biological barrier membranes, select biodegradable raw materials such as chitosan, collagen, polylactic acid and the like as a base material of the membrane, mix antibacterial drugs with the base material, and carry the drugs in the biological membrane by solution casting, electrostatic spinning and other methods. The drug existing on the surface of the biological membrane material can be suddenly released, and most of the drug is released at the stage, so that the drug can be continuously released from the membrane after the sudden release due to the interaction between the drug and the material matrix. In recent years, microfluidic technology has been rapidly developed, and has become an important tool in the biomedical research field with numerous advantages. The microfluidic technology is applied to improvement of biological barrier membranes, the microfluidic biological barrier membranes with medicine storage pools and micro-channel structures are constructed, medicines are stored in the medicine storage pools, and the control effect on fluid can be achieved through the precisely designed micro-channel structures.
In summary, developing a microfluidic biological barrier membrane that can slowly release drugs is of great importance in effectively reducing the risk of postoperative infection.
Disclosure of Invention
The invention aims to provide a micro-fluidic biological barrier membrane capable of slowly releasing medicines, which has simple manufacturing process, is different from the traditional medicine carrying membrane, is a micro-fluidic chip comprising a medicine storage tank and a medicine inlet and outlet channel, is used for storing medicines in the medicine storage tank and releasing medicines through a medicine release outlet, can continuously and slowly release antibacterial medicines for 5 days, effectively relieves the early burst release phenomenon, and can control the medicine release rate so as to overcome the defects in the prior art.
The technical scheme of the invention is as follows:
the micro-fluidic biological barrier membrane for releasing medicine has three layers, including medicine releasing layer, middle connecting layer and non-medicine releasing bottom layer.
The medicine release layer is provided with a medicine inlet, a medicine release outlet and a positioning hole; the middle connecting layer is provided with a positioning hole, two symmetrical and unconnected medicine storage tanks are arranged at the middle part of the middle connecting layer, and a medicine inlet channel and a medicine release outlet channel which are communicated with the medicine storage tanks are arranged; the non-drug release bottom layer is only provided with positioning holes; the three-layer structure is bonded together through the positioning holes of each layer, and the upper side and the lower side of the middle connecting layer are respectively attached to the drug release layer and the non-drug release bottom layer.
And a porous chitosan membrane is placed at the drug release outlet of the microfluidic biological barrier membrane.
The medicine storage tanks are two symmetrical and non-connected semicircular medicine storage tanks, a medicine inlet channel and a medicine release outlet channel which are communicated with the semicircular medicine storage tanks are arranged on semicircular arcs of the semicircular medicine storage tanks, and a medicine inlet channel and two medicine release outlet channels are respectively arranged on each semicircular medicine storage tank, and the positions of the two channels are not fixed.
The area of the medicine storage pool on the intermediate connecting layer accounts for 1/3-1/2 of the total area of the intermediate connecting layer.
The ratio of the width to the length of the drug inlet channel is 1/3.
The ratio of the width to the length of the drug release outlet channel is 1/2.
The drug release layer, the middle connecting layer and the non-drug release bottom layer are made of PLA biodegradable materials.
The medicine storage pool is internally provided with medicine liquid and medicine carrying nano microspheres.
The concrete explanation is as follows:
the medicine release layer is provided with a medicine inlet, a medicine release outlet and a positioning hole; the middle connecting layer is provided with a positioning hole, two symmetrical and disconnected semicircular medicine storage tanks are cut at the middle part of the middle connecting layer, a medicine inlet channel and a medicine release outlet channel which are communicated with the semicircular medicine storage tanks are cut on the semicircular arc of the semicircular medicine storage tanks, and each semicircular medicine storage tank is provided with one medicine inlet channel and two medicine release outlet channels, and the positions of the two channels are not fixed, so that the medicine release point can be changed by changing the positions of the medicine release outlet channels; the non-drug release bottom layer is only provided with positioning holes. The three-layer structure is bonded together through the positioning holes of each layer, and the upper side and the lower side of the middle connecting layer are respectively bonded with the drug release layer and the non-drug release bottom layer, so that a drug storage pool area is formed on the microfluidic biological barrier membrane, and drugs are injected through the drug inlets on the drug release layer, enter the drug storage pool through the drug inlet channels and are released from the drug release outlets of the drug release layer through the drug release outlet channels; in addition, the porous chitosan film is placed at the drug release outlet of the microfluidic biological barrier film, the porous chitosan film can play a role of a micro valve, and the contact area of the drug and the external environment can be changed by changing the porosity of the porous chitosan film, so that the effect of controlling the drug release rate is achieved.
Aiming at the defect that the biological barrier membrane in the guided bone regeneration operation can only repair defects by virtue of the growth potential of the organism and cannot effectively prevent complications such as postoperative infection, the invention designs the microfluidic biological barrier membrane capable of slowly releasing medicines. A micro-channel system is designed, a medicine storage pool structure is arranged in the system, and each medicine storage pool is connected with a medicine inlet channel and a medicine outlet channel; the medicine pool is filled with medicine liquid and medicine carrying microspheres, and the porous chitosan film is placed above each medicine release outlet hole, so that the porous chitosan film at the outlet reduces the contact area of the medicine liquid and the external environment, the medicine release time is further prolonged, and the medicine carrying microspheres can supplement medicine amount for the medicine storage pool in the medicine release process; compared with the single local application, the slow-release drug-carrying microfluidic biological barrier membrane effectively reduces the early-stage burst release phenomenon, and can maintain the effective drug concentration for a period of time.
Compared with the existing biological barrier film, the microfluidic biological barrier film capable of slowly releasing the medicine has the following advantages:
the micro-fluidic biological barrier membrane comprises a micro-channel structure, so that the medicine is stored in the medicine storage pool and is released through the medicine release outlet channel, and the porous chitosan membrane is placed at the medicine release outlet hole, so that the contact area between the medicine and the external environment is reduced by the porous chitosan membrane at the outlet, the release rate can be further slowed down, the medicine release time is prolonged, and the phenomenon of early-stage medicine burst is effectively relieved;
the porosity of the chitosan film placed at the drug release outlet hole can be changed, so that the control effect on the drug release rate can be achieved;
because the medicine solution and the medicine carrying nano-microsphere exist in the medicine storage pool at the same time, the medicine carrying microsphere can supplement medicine quantity for the medicine storage pool in the medicine release process, and the effective medicine concentration is maintained.
Drawings
FIG. 1 is a schematic structural view of a microfluidic biological barrier membrane according to the present invention; the microfluidic biological barrier membrane is of a three-layer structure, namely a 1-drug inlet, a 2-drug release layer, a 3-positioning hole, a 4-drug release outlet, a 5-intermediate connecting layer, a 6-drug storage tank, a 7-non-drug release bottom layer and an 8-porous chitosan membrane;
FIG. 2 is a top view of the morphology of a first drug release layer in a microfluidic biological barrier membrane according to the present invention; 1-drug inlet, 3-locating hole, 4-drug release outlet, d 1-drug release outlet hole diameter, d 2-drug inlet hole diameter, R1-biological barrier membrane radius;
FIG. 3 is a top view of the morphology of the second intermediate tie layer in the microfluidic biological barrier membrane according to the invention; 1-medicine inlet, 3-positioning hole, 4-medicine release outlet, 6-medicine storage pool, R2-medicine storage pool radius, L1, w 1-medicine inlet channel length and width, L2, w 2-medicine release outlet channel length and width;
FIG. 4 is a top view of the morphology of a third non-drug release substrate in the microfluidic biological barrier membrane according to the present invention; 3-positioning holes, d 3-positioning hole diameters;
FIG. 5 is a graph showing cumulative drug release when chitosan films of different porosities are respectively placed at drug release outlets;
fig. 6 is a graph of drug release with varying internal and external concentration gradients.
Detailed Description
The invention is further described below with reference to the drawings and specific examples.
Example 1
As a first example of the microfluidic biological barrier membrane for drug release in the present invention, the structure of the microfluidic biological barrier membrane is shown in fig. 1. The barrier membrane is of a three-layer structure, and is respectively a drug release layer, a middle connecting layer and a non-drug release bottom layer. Each layer is provided with four positioning holes so as to facilitate alignment and lamination between layers, the middle part of the middle connecting layer is cut into two symmetrical and unconnected semicircular medicine storage tanks, a medicine inlet channel and two medicine release outlet channels which are communicated with the semicircular medicine storage tanks are respectively cut on the semicircular arc of each semicircular medicine storage tank, the two medicine release outlet channels are axially arranged and form an included angle of 180 degrees, the medicine inlet channels are radially arranged and form an included angle of 90 degrees with the medicine release outlet channels, the positions of the medicine inlet and outlet channels on the two medicine storage tanks are the same, and a medicine inlet and a medicine release outlet are arranged at the corresponding positions of the medicine release layers. As shown in FIG. 2, the drug release layer is provided with a drug inlet and a drug outlet and a positioning hole, namely a 1-drug inlet, a 3-positioning hole, a 4-drug release outlet, a d 1-drug release outlet hole diameter, a d 2-drug inlet diameter and a R1-barrier membrane radius. The intermediate linkage layer is provided with two symmetrical and non-connected semicircular medicine storage tanks, each medicine storage tank is connected with a medicine inlet channel and two medicine release outlet channels, as shown in fig. 3, and the main structure comprises: 1-medicine inlet, 3-locating hole, 4-medicine release outlet, 6-medicine storage pool, R2-medicine storage pool radius, L1, w 1-medicine inlet channel length, width, L2, w 2-medicine release outlet channel length, width. As shown in figure 4, the non-drug release bottom layer is only provided with a positioning hole, a 3-positioning hole and a d 3-positioning hole diameter. The manufacturing process of the microfluidic biological barrier membrane comprises the following steps:
the method comprises the steps of (1) manufacturing a medicine inlet (1), a medicine release outlet (4) and a positioning hole (3) on a medicine release layer (2) through a laser cutting method;
(2) Manufacturing an intermediate connecting layer (5) by using a 3D printing technology to form a medicine storage pool (6) area, a fluid channel and a positioning hole (3);
(3) A positioning hole (3) is manufactured on the non-drug release bottom layer (7) by a laser cutting method;
(4) Cutting porous chitosan membrane into round shape;
(5) The drug release layer, the middle connecting layer, the non-drug release bottom layer and the porous chitosan membrane are bonded into a whole by using biological glue, wherein the porous chitosan membrane is placed on the drug release outlets of the middle connecting layers, the diameter of the circular porous chitosan membrane is larger than that of the outlet holes, so that the circular porous chitosan membrane completely covers the drug release outlets, and the porous chitosan membrane is fixed between the middle connecting layers and the drug release layers (as shown in figure 1), so that the microfluidic biological barrier membrane for releasing the drugs is obtained.
The assembly sequence of the microfluidic biological barrier membrane is that firstly, a non-drug release bottom layer (7) is bonded with an intermediate connecting layer (5), then a porous chitosan membrane is placed on each drug release outlet of the intermediate connecting layer, the diameter of the circular porous chitosan membrane is larger than that of an outlet hole, so that the circular porous chitosan membrane completely covers the drug outlet, and the porous chitosan membrane is fixed between the intermediate connecting layer (5) and the drug release layer (2); and finally, bonding the drug release layer and the middle connecting layer to obtain the microfluidic biological barrier membrane. The two sides of the middle connecting layer are respectively attached to the drug release layer and the non-drug release bottom layer, so that a drug storage pool area is formed on the microfluidic biological barrier membrane, and drugs are injected through a drug inlet on the drug release layer, enter the drug storage pool through a drug inlet channel and are released from a drug release outlet of the drug release layer through a drug release outlet channel.
The thickness of the middle connecting layer of the microfluidic biological barrier membrane for drug release described in the embodiment is 0.8mm, and the thicknesses of the drug release layer and the non-drug release bottom layer are both 0.2mm.
The microfluidic biological barrier membrane for drug release described in this example has a radius of 17.5mm and a semi-circular drug reservoir of 10mm, the reservoir area being approximately 1/3 of the total barrier membrane area.
The micro-fluidic biological barrier membrane for drug release described in this example has a drug inlet straight channel length of 1.2mm, a drug inlet width of 0.4mm, and a drug inlet orifice diameter of 1mm.
The microfluidic biological barrier membrane for drug release described in this example was 2.0mm long, 1.0mm wide, and 1.5mm in diameter for the drug release outlet.
The micro-fluidic biological barrier membrane for drug release described in this example has a positioning hole diameter of 1mm.
Example 2
In this embodiment, the size of the micro-channel in the micro-fluidic bio-barrier film is changed, and the manufacturing process is as follows:
the method comprises the steps of (1) manufacturing a medicine inlet (1), a medicine release outlet (4) and a positioning hole (3) on a medicine release layer (2) through a laser cutting method;
(2) Manufacturing an intermediate connecting layer (5) by using a 3D printing technology to form a medicine storage pool (6) area, a fluid channel and a positioning hole (3);
(3) A positioning hole (3) is manufactured on the non-drug release bottom layer (7) by a laser cutting method;
(4) Cutting porous chitosan membrane into round shape;
(5) The drug release layer, the middle connecting layer, the non-drug release bottom layer and the porous chitosan membrane are bonded into a whole by using biological glue, wherein the porous chitosan membrane is placed on each drug release outlet of the middle connecting layer, the diameter of the circular porous chitosan membrane is larger than that of the outlet hole, so that the circular porous chitosan membrane completely covers the drug release outlet, and the porous chitosan membrane is fixed between the middle connecting layer and the drug release layer (as shown in figure 1), so that the drug slow-release microfluidic biological barrier membrane is obtained.
The thickness of the middle connecting layer of the microfluidic biological barrier membrane for drug release described in the embodiment is 0.8mm, and the thicknesses of the drug release layer and the non-drug release bottom layer are both 0.2mm.
The microfluidic biological barrier membrane for drug release described in this example has a 7mm radius barrier membrane and a 5mm radius semicircular reservoir, the reservoir area being approximately 1/2 of the total barrier membrane area.
The microfluidic biological barrier membrane for drug release described in this example was characterized by a drug inlet straight channel length of 0.9mm, a drug inlet width of 0.3mm, and a drug inlet orifice diameter of 0.6mm.
The microfluidic biological barrier membrane for drug release described in this example was 1.4mm long and 0.7mm wide in the straight channel of the drug release outlet and 1mm in the diameter of the drug release outlet.
The micro-fluidic biological barrier membrane for drug release described in this example has a positioning hole diameter of 1mm.
Example 3
As a third embodiment, the present invention provides a method for releasing a drug in the microfluidic biological barrier membrane, by which slow release of the drug can be achieved. The assembly sequence of the microfluidic biological barrier membrane is that firstly, a non-drug release bottom layer and an intermediate connecting layer are bonded, then a porous chitosan membrane is placed above each drug release outlet hole of the intermediate connecting layer, the diameter of the circular porous chitosan membrane is larger than that of the outlet holes, so that the circular porous chitosan membrane completely covers the drug release outlet, and the porous chitosan membrane is fixed between the intermediate connecting layer and the drug release layer; and finally, bonding the drug release layer and the middle connecting layer. After the microfluidic biological barrier membrane is prepared, a certain amount of minocycline medicine powder is taken, cheng Minuo of minocycline solution is prepared, the minocycline solution is sucked into an injector, the minocycline solution is injected into a medicine storage tank along a medicine inlet by the injector until the medicine storage tank is filled with liquid and no bubbles exist in the medicine storage tank, and after the medicine injection is finished, the medicine inlet is sealed to prevent the liquid from leaking from the inlet.
The microfluidic biological barrier membrane (barrier membrane size identical to that in example 1) was placed in a beaker containing 10mL of PBS (pH 7.4) solution and fixed to the bottom of the beaker, the drug release layer was placed up and stored in the absence of light at 37 ℃. Because the inner and outer concentrations of the biological barrier membrane are different, the liquid medicine in the medicine storage pool diffuses from the outlet until the inner and outer concentrations are equal to reach balance; the porous chitosan membrane at the outlet reduces the contact area of the liquid medicine and the external environment, and can prolong the drug release time. 1mL of the sample was sampled at regular intervals, 1mL of PBS (pH 7.4) solution was added after each sampling, and the sample concentration was measured by high performance liquid chromatography and the cumulative release content was calculated. The experiment is divided into three groups, namely a small-aperture chitosan membrane is placed at a 1-drug release outlet, a medium-aperture chitosan membrane is placed at a 2-drug release outlet, and a large-aperture chitosan membrane is placed at a 3-drug release outlet.
The cumulative release curve shows (as shown in fig. 5), when the pore diameter of the chitosan membrane at the drug release outlet is changed, the drug release rate is changed, and as the pore diameter of the chitosan membrane is reduced, the drug release rate is slowed down, and when the chitosan membrane with the smallest pore diameter is placed at the drug release outlet, the early-stage drug burst phenomenon is effectively relieved, which indicates that the porous chitosan membranes with different porosities are placed at the drug release outlet of the microfluidic biological barrier membrane, so that the effect of controlling the drug release rate can be achieved.
Example 4
In this example, a liquid change operation was performed in the drug release experiment. After the microfluidic biological barrier membrane is prepared (a chitosan membrane with the smallest aperture is selected at a drug release outlet), a certain amount of minocycline drug powder is taken, cheng Minuo of minocycline solution is prepared, the minocycline solution is sucked into an injector, the minocycline solution is injected into a drug storage tank along a drug inlet by the injector until the drug tank is filled with liquid and no bubble exists in the tank, and after the drug injection is finished, the drug inlet is sealed to prevent the liquid from leaking from the inlet. The drug-loaded microfluidic biological barrier membrane (barrier membrane size same as in example 1) was placed in a beaker containing 10mL of PBS (pH 7.4) solution and fixed to the bottom of the beaker, the drug release layer was placed up and stored in the absence of light at 37 ℃. 1mL of the sample was sampled at regular intervals, 1mL of PBS (pH 7.4) solution was added after each sampling, 50% was exchanged every 24 hours, and the sample concentration was measured by high performance liquid chromatography and the cumulative release content was calculated. The cumulative release curve (shown in fig. 6) shows that the pure minocycline liquid medicine is loaded in the microfluidic biological barrier membrane, and the drug release is accelerated due to the liquid change operation, so that the drug release is basically stopped after the second liquid change (48 h), and in order to improve the phenomenon, the drug-loaded nano-microsphere is introduced. In the experiment, the drug-loaded nano-microspheres are loaded in the microfluidic biological barrier membrane, and the accumulated release curve (shown in figure 6) shows that the drug in the drug-loaded microspheres can be released in a large amount in the later period, so that the drug-loaded nano-microspheres and the liquid medicine are injected into the microfluidic biological barrier membrane together, the drug-loaded microspheres can supplement the drug content of the drug storage tank in the later period of the drug release process, the drug release time is prolonged, and the combination can continuously release the drug for 120 hours under the condition of changing the liquid as shown in figure 6.
The above embodiments are merely illustrative of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention, and any person skilled in the art should make various modifications and improvements to the technical solution of the present invention without departing from the spirit of the design of the present invention, which falls within the scope of protection defined by the claims of the present invention.
Claims (6)
1. The microfluidic biological barrier membrane for releasing the medicine is characterized by comprising a three-layer structure, namely a medicine release layer, a middle connecting layer and a non-medicine release bottom layer; the medicine release layer is provided with a medicine inlet, a medicine release outlet and a positioning hole; the middle connecting layer is provided with a positioning hole, two symmetrical and unconnected medicine storage tanks are arranged at the middle part of the middle connecting layer, and a medicine inlet channel and a medicine release outlet channel which are communicated with the medicine storage tanks are arranged; the non-drug release bottom layer is only provided with positioning holes; bonding the three-layer structure together through the positioning holes of each layer, and respectively attaching the upper side and the lower side of the middle connecting layer with the drug release layer and the non-drug release bottom layer; a porous chitosan membrane is placed at a drug release outlet of the microfluidic biological barrier membrane; the medicine liquid and the medicine carrying nanometer microsphere exist in the medicine storage pool at the same time.
2. The microfluidic biological barrier membrane for drug release according to claim 1, wherein the drug storage tank is two symmetrical and unconnected semicircular drug storage tanks, a drug inlet channel and a drug release outlet channel which are communicated with the semicircular drug storage tank are arranged on a semicircular arc of the semicircular drug storage tank, and one drug inlet channel and two drug release outlet channels are respectively arranged on each semicircular drug storage tank, and the positions of the two channels are not fixed.
3. The microfluidic biological barrier membrane for drug release according to claim 2, wherein the area of the drug reservoir on the intermediate connection layer is 1/3-1/2 of the total area of the intermediate connection layer.
4. The microfluidic biological barrier membrane for drug release of claim 2, wherein the ratio of the drug inlet channel width to the length is 1/3.
5. The microfluidic biological barrier membrane for drug release of claim 2, wherein the ratio of the drug release outlet channel width to the length is 1/2.
6. The microfluidic biological barrier membrane for drug release according to claim 2, wherein the drug release layer, the intermediate connection layer and the non-drug release bottom layer are made of PLA biodegradable materials.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1857730A (en) * | 2006-03-30 | 2006-11-08 | 西安交通大学 | Degradable implated medicine release-controlling carrier with micropores and cavities and its preparing process |
| KR20130021165A (en) * | 2011-08-22 | 2013-03-05 | 서울대학교산학협력단 | A microchip for sustained drug delivery |
| JP2020156968A (en) * | 2019-03-28 | 2020-10-01 | 国立大学法人東北大学 | Expansion controllable medicine sustained-release sheet utilizing four layered structure |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1857730A (en) * | 2006-03-30 | 2006-11-08 | 西安交通大学 | Degradable implated medicine release-controlling carrier with micropores and cavities and its preparing process |
| KR20130021165A (en) * | 2011-08-22 | 2013-03-05 | 서울대학교산학협력단 | A microchip for sustained drug delivery |
| JP2020156968A (en) * | 2019-03-28 | 2020-10-01 | 国立大学法人東北大学 | Expansion controllable medicine sustained-release sheet utilizing four layered structure |
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