CN101879427B - Doxorubicin hydrochloride-carrying natural polymer-poly(3-benzene acid acrylamide) composite nanospheres, manufacturing method and application thereof - Google Patents
Doxorubicin hydrochloride-carrying natural polymer-poly(3-benzene acid acrylamide) composite nanospheres, manufacturing method and application thereof Download PDFInfo
- Publication number
- CN101879427B CN101879427B CN201010213156XA CN201010213156A CN101879427B CN 101879427 B CN101879427 B CN 101879427B CN 201010213156X A CN201010213156X A CN 201010213156XA CN 201010213156 A CN201010213156 A CN 201010213156A CN 101879427 B CN101879427 B CN 101879427B
- Authority
- CN
- China
- Prior art keywords
- microsphere
- poly
- boric acid
- phenyl boric
- natural polymer
- 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
Images
Abstract
The invention discloses natural polymer-poly(3-benzene acid acrylamide) composite nanospheres. The surfaces of the natural polymer-poly(3-benzene acid acrylamide) composite nanospheres are hydrophilic natural polymers; the interiors are hydrophobic poly(3-benzene acid acrylamide); the number average molecular weight of the natural polymer is in a range of between 2,000 and 100,000; the content of the natural polymer is 5 to 70 percent of the mass of the composite nanospheres; the number average molecular weight of the poly(3-benzene acid acrylamide) is in a range of between 1,000 and 10,000; the content of the poly(3-benzene acid acrylamide) is 30 to 95 percent of the mass of the composite nanospheres; and the average grain diameter of the composite nanospheres is of between 40 and 100 nanometers. The composite nanospheres of the invention have the characteristics of high biocompatibility and stable chemical properties. The composite nanospheres of the invention can be used as a medicament carrier, has a sustained-release effect, and can be used as a carrying agent in a boron neutron capture therapy. The invention also discloses a manufacturing method for the composite nanospheres.
Description
Technical field
The present invention relates to a kind of biodegradable natural polymer-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere, can be used as boron neutron capture therapy, also can be used as pharmaceutical carrier.
Background technology
Boron neutron capture therapy (BNCT) is the methods for the treatment of of destroying cancer cell by the nuclear reaction in the tumour cell.Its treatment principle is first to tumour patient injection isotope
10Boron, boron are assembled in tumour cell after entering in the body, and other Tissue distribution seldom.The compound of this boracic is nontoxic to human body, and cancer is not had result for the treatment of yet.With a kind of thermal neutron radiation exposure tumor locus, during neutron exposure 1
101 neutron of boron Atomic absorption becomes
11Nuclear fission also occurs in the boron atom, the fission discharge the α particle (
4He) and lithium atom (
7Li).The α particle is the extremely strong ray of lethality, effective kill tumor cell, and effective equally to anoxic tumour cell and interkinesis tumour cell.Because only about 10 microns of alpha partical ranges, i.e. cell dia, so can only kill the tumour cell that nuclear reaction occurs, on the surrounding normal cell without impact, thereby reach the purpose of protection surrounding health tissue at cellular level.And as the agent of carrying of BNCT, should possess following characteristics:
1, carry the agent avirulence, to the selective height of tumour, after the administration concentration of medicine in tumour be normal structure concentration 3-4 doubly;
2, the concentration of boron must reach 20 microgram/grams in the tumor tissues;
3, carry agent during the treatment and in tumor tissues, keep certain concentration, in body He the blood, remove fast.
At present extensive use be that low molecule and macromolecule boron carry agent two large classes.Low molecule boron carries the agent extensive use is sulfydryl ten diborane disodium salts (BSH) and to dihydroxy boron acyl phenylalanine (BPA).It mainly is the boronation monoclonal antibody that high molecular boron carries agent.Studies show that also do not have a kind of boron that meets above-mentioned requirements fully to carry agent at present, mainly is owing to unavoidably there is boron to carry the existence of agent in the normal structure, is difficult to effectively solve the problem that normal structure preserves from.Therefore, seek bio-compatible and biodegradable boron and carry agent, the boron that improves again tumor locus when reducing the normal structure absorption carries agent concentration and arouses widespread concern.
ADMh is a kind of antitumor antibiotics, is the anthracycline anti-malignant-tumor agent of commonly using clinically.Can suppress the synthetic of RNA and DNA, wherein the inhibitory action to RNA is the strongest, and antitumor spectra is wide, and kinds of tumors is had effect, belongs to cell cycle nonspecific agent (CCNSA), and the tumour cell of various growth cycles is had killing action.Mainly be applicable to leukaemia, all effective to ALL and chronic myeloid leukemia, to breast cancer, sarcoma, lung cancer, carcinoma of urinary bladder, thyroid adenoma, chorioepithelioma, prostate cancer, carcinoma of testis, cancer of the stomach, other various cancers of liver cancer etc. have certain curative effect, and many and other antineoplastics are united use.But the toxic and side effect of adriamycin is more serious, and such as leucocyte and decrease of platelet, cardiac toxic shows as arrhythmia cordis, feels sick, and anorexia, medicine overflow outside the blood vessel can cause tissue ulcer and necrosis.In addition, redness can appear in urine after the medication.Studies have shown that, after antineoplastic is by all means administration, reach that certain blood concentration is distributed in whole body and the therapeutic action played.But the molecular weight ratio of most antineoplastics is lower, and easily diffusion causes relatively average Tissue distribution in vivo, often produces toxic and side effect in treatment.Therefore, seek bio-compatible and biodegradable adriamycin carrier, the drug concentration that does not reduce again even improve tumor locus when reducing the normal structure toxic and side effect arouses widespread concern.
Along with the development of biological medicine nanometer technology, so that the drug delivery system of biodegradable natural polymer nanoparticle becomes the emphasis of Effect of Anti tumour medicine.The vascular system of tumor locus has the permeability higher than normal position (EPR) effect, and the natural polymer nano particle can by this effect,, reach the effect of " passive target " drug delivery in diseased region enrichments such as tumours.Drug-carried nanometer removed from blood circulation system by the macrophage phagocytic of reticuloendothelial system, so the curative effect of medicine is very restricted after entering body.The natural polymer nano particle except possess that the conventional medicament delivery system has such as improving drug solubility, increasing the advantages such as medicine stability and slowly-releasing, can also change Tissue distribution and the metabolism of medicine, improve drug effect and reduce system's toxic and side effect of medicine, have great using value at clinicing aspect.
Phenyl boric acid can form reversible five-membered ring or the borate of hexatomic ring with the polyol of 1,2 glycol or 1,3 glycol, can also coordination be arranged with amino.And occurring in nature contains a large amount of polyols, can form borate with phenyl boric acid, and this process also is a reversible process.Because the response characteristic of phenyl boric acid, it can be widely used in detects, separates, purifies, and can also be used for the self-discipline delivery system or regulate vital movement.Up to now, natural polymer-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere there is not yet report.
Summary of the invention
The object of the present invention is to provide a kind of bio-compatible, can be biodegradable, may be used for boron neutron capture therapy, useful as drug carrier natural polymer Nano microsphere and preparation method thereof.
Technical scheme of the present invention is as follows:
A kind of natural polymer-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere, its surface is hydrophilic natural polymer, inside is hydrophobic poly-(3-acrylamido phenyl boric acid), the number-average molecular weight of natural polymer is in the 3000-100000 scope, content is the 5%-70% of composite nano-microsphere quality, the number-average molecular weight of poly-(3-acrylamido phenyl boric acid) is in the 2000-4000 scope, and content is the 30%-95% of composite nano-microsphere quality.The average grain diameter of Nano microsphere is the 40-100 nanometer.
The natural polymer of the above-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere, described natural polymer can be glucan, shitosan, hydroxypropyl cellulose, alginic acid, heparin, bovine serum albumin.
A kind of method for preparing above-mentioned natural polymer-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere, it comprises the steps:
After step 2. dissolve complete and the cooling, add radical initiator and regulate pH to 3-7 with NaOH, reaction is 1-4 hour under 60-90 ℃ of stirring, formation water nanoparticle dispersion liquid after reaction is finished.
The method for making of above-mentioned natural polymer-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere, described initator can be potassium peroxydisulfate or 4,4 '-azo (4-cyanopentanoic acid).
A kind of natural polymer that is loaded with ADMh-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere, it be above-mentioned natural polymer-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere as carrier, be loaded with the natural polymer that is loaded with ADMh-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere of ADMh of the 5-10% of composite nano-microsphere quality.
A kind of method for preparing the natural polymer that is loaded with ADMh-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere, it is that the aqueous dispersions of above-mentioned natural polymer-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere is regulated pH behind 5-9 with NaOH, stir the lower ADMh that adds, the ratio of the amount of substance of phenyl boric acid unit is 0.1 in ADMh and the Nano microsphere: 1-1: 1, reaction is after 12-72 hour under stirring at room, dialysis, namely obtain being loaded with the natural polymer of ADMh-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere, wherein, ADMh accounts for the 5-10% of composite nano-microsphere quality.
The natural polymer that preparation method of the present invention makes-gather (3-acrylamido phenyl boric acid) composite nano-microsphere particle diameter than homogeneous, good dispersion.
The natural polymer of the present invention's preparation-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere can be used as pharmaceutical carrier, also may be as the agent of carrying of boron neutron capture therapy.
Natural polymer of the present invention-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere and need packaging medicine through stirring, absorption, dialysis obtains being enclosed with the natural polymer of medicine-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.
The natural polymer that is loaded with ADMh of the present invention-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere has very strong drug slow release function.
The invention provides the preparation method of the natural polymer that a kind of average grain diameter is 40-100nm-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.Composite nano-microsphere good biocompatibility of the present invention, stable chemical nature.Composite nano-microsphere of the present invention can be used as pharmaceutical carrier, also may be as the agent of carrying of boron neutron capture therapy.Load of the present invention has the composite nano-microsphere of ADMh, has very strong drug slow release function.
Description of drawings
Fig. 1 is release in vitro curve (the ■ pH7.4 of the glucan that is loaded with adriamycin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
● pH4.0).
Fig. 2 is that glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere is to gastric carcinoma cells MKN-28 vitro cytotoxicity experimental result.
Fig. 3 is that the glucan that is loaded with adriamycin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere is to human cervical carcinoma cell Hela vitro cytotoxicity experimental result.
The specific embodiment
Further illustrate content of the present invention below in conjunction with embodiment, but these embodiment do not limit protection scope of the present invention.
Embodiment 1: the preparation of glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
In the 25ml stirring reactor, be that 152 milligrams of glucans of 3000 are dissolved in 12 ml distilled waters with 90 milligrams of 3-acrylamido phenyl boric acids and number-average molecular weight.Behind the cool to room temperature, add 9.4 milligram 4,4 '-azo (4-cyanopentanoic acid) initator.Be warmed up to 80 ℃, initiated polymerization 2 hours obtains the aqueous solution of glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.Stop reaction, system temperature is down to room temperature, with the aqueous dispersions dialysis 24 hours of packing in the bag filter (the Cut-off molecular weight is 12000), remove unreacted monomer in the system.The average grain diameter of the Nano microsphere that records by dynamic light scattering is 72.5 ± 2.0nm.Wherein natural polymer accounts for 9.1%, and poly-(3-acrylamido phenyl boric acid) accounts for 90.9%.The number-average molecular weight of poly-(3-acrylamido phenyl boric acid) is 2000.
Embodiment 2: the preparation of glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
In the 25ml stirring reactor, be that 76 milligrams of glucans of 3000 are dissolved in 12 ml distilled waters with 90 milligrams of 3-acrylamido phenyl boric acids and number-average molecular weight.Behind the cool to room temperature, add 9.4 milligram 4,4 '-azo (4-cyanopentanoic acid) initator.Be warmed up to 80 ℃, initiated polymerization 2 hours obtains the aqueous solution of glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.Stop reaction, system temperature is down to room temperature filters, dialysis is 24 hours in the bag filter (the Cut-off molecular weight is 12000) of after the filtration aqueous dispersions being packed into, removes unreacted monomer in the system.The average grain diameter of the Nano microsphere that records by dynamic light scattering is 77.4 ± 2.1nm, and wherein natural polymer accounts for 4.2%, and poly-(3-acrylamido phenyl boric acid) accounts for 95.8%.The number-average molecular weight of poly-(3-acrylamido phenyl boric acid) is 2000.
Embodiment 3: the preparation of glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
In the 25ml stirring reactor, be that 38 milligrams of glucans of 3000 are dissolved in 12 ml distilled waters with 90 milligrams of 3-acrylamido phenyl boric acids and number-average molecular weight.Behind the cool to room temperature, add 9.4 milligram 4,4 '-azo (4-cyanopentanoic acid) initator.Be warmed up to 80 ℃, initiated polymerization 2 hours obtains the aqueous solution of glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.Stop reaction, system temperature is down to room temperature filters, dialysis is 24 hours in the bag filter (the Cut-off molecular weight is 12000) of after the filtration aqueous dispersions being packed into, removes unreacted monomer in the system.The average grain diameter of the Nano microsphere that records by dynamic light scattering is 65.1 ± 0.1nm, and wherein natural polymer accounts for 2.5%, and poly-(3-acrylamido phenyl boric acid) accounts for 97.5%.The number-average molecular weight of poly-(3-acrylamido phenyl boric acid) is 2500.
Embodiment 4: the preparation of glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
In the 25ml stirring reactor, be that 304 milligrams of glucans of 3000 are dissolved in 12 ml distilled waters with 90 milligrams of 3-acrylamido phenyl boric acids and number-average molecular weight.Behind the cool to room temperature, add 9.4 milligram 4,4 '-azo (4-cyanopentanoic acid) initator.Be warmed up to 80 ℃, initiated polymerization 2 hours obtains the aqueous solution of glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.Stop reaction, system temperature is down to room temperature filters, dialysis is 24 hours in the bag filter (the Cut-off molecular weight is 12000) of after the filtration aqueous dispersions being packed into, removes unreacted monomer in the system.The average grain diameter of the Nano microsphere that records by dynamic light scattering is 98.8 ± 1.6nm.Wherein natural polymer accounts for 14.3%, and poly-(3-acrylamido phenyl boric acid) accounts for 85.7%.The number-average molecular weight of poly-(3-acrylamido phenyl boric acid) is 2000.
Embodiment 5: the preparation of glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
In the 25ml stirring reactor, be that 152 milligrams of glucans of 40000 are dissolved in 12 ml distilled waters with 90 milligrams of 3-acrylamido phenyl boric acids and number-average molecular weight.Behind the cool to room temperature, add 6 milligrams of potassium peroxydisulfate initators.Be warmed up to 80 ℃, initiated polymerization 2 hours obtains the aqueous solution of glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.Stop reaction, system temperature is down to room temperature filters, dialysis is 24 hours in the bag filter (the Cut-off molecular weight is 100000) of after the filtration aqueous dispersions being packed into, removes unreacted monomer in the system.The average grain diameter of the Nano microsphere that records by dynamic light scattering is 98.8 ± 1.6nm, and wherein natural polymer accounts for 9.1%, and poly-(3-acrylamido phenyl boric acid) accounts for 90.9%.The number-average molecular weight of poly-(3-acrylamido phenyl boric acid) is 2000.
Embodiment 6: the preparation of bovine serum albumin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
In the 50ml stirring reactor, be that 40 milligrams of bovine serum albumins of 66000 are dissolved in 12 ml distilled waters with 60 milligrams of 3-acrylamido phenyl boric acids and number-average molecular weight.Behind the cool to room temperature, add 8.5 milligram 4,4 '-azo (4-cyanopentanoic acid) initator.Be warmed up to 80 ℃, initiated polymerization 2 hours obtains the aqueous solution of bovine serum albumin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.Stop reaction, system temperature is down to room temperature filters, dialysis is 24 hours in the bag filter (the Cut-off molecular weight is 100000) of after the filtration aqueous dispersions being packed into, removes unreacted monomer in the system.The average grain diameter of the Nano microsphere that records by dynamic light scattering is 42.5 ± 1.0nm, and wherein natural polymer accounts for 74%, and poly-(3-acrylamido phenyl boric acid) accounts for 26%.The number-average molecular weight of poly-(3-acrylamido phenyl boric acid) is 3000.
Embodiment 7: the preparation of shitosan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
In the 25ml stirring reactor, be that 120 milligrams of shitosans of 100000 are dissolved in 12 ml distilled waters with 90 milligrams of 3-acrylamido phenyl boric acids and number-average molecular weight.Behind the cool to room temperature, add 6 milligrams of potassium peroxydisulfate initators.Be warmed up to 80 ℃, initiated polymerization 2 hours obtains the aqueous solution of shitosan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.Stop reaction, system temperature is down to room temperature filters, dialysis is 24 hours in the bag filter (the Cut-off molecular weight is 100000) of after the filtration aqueous dispersions being packed into, removes unreacted monomer in the system.The average grain diameter of the Nano microsphere that records by dynamic light scattering is 92.5 ± 2.0nm, and wherein natural polymer accounts for 42%, and poly-(3-acrylamido phenyl boric acid) accounts for 58%.The number-average molecular weight of poly-(3-acrylamido phenyl boric acid) is 3500.
Embodiment 8: the preparation of alginic acid-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
In the 25ml stirring reactor, be that 60 milligrams of alginic acids of 50000 are dissolved in 12 ml distilled waters with 90 milligrams of 3-acrylamido phenyl boric acids and number-average molecular weight.Behind the cool to room temperature, add 9 milligram 4,4 '-azo (4-cyanopentanoic acid) initator.Be warmed up to 80 ℃, initiated polymerization 2 hours obtains the aqueous solution of alginic acid-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.Stop reaction, system temperature is down to room temperature filters, dialysis is 24 hours in the bag filter (the Cut-off molecular weight is 100000) of after the filtration aqueous dispersions being packed into, removes unreacted monomer in the system.The average grain diameter of the Nano microsphere that records by dynamic light scattering is 100.5 ± 2.0nm, and wherein natural polymer accounts for 32%, and poly-(3-acrylamido phenyl boric acid) accounts for 68%.The number-average molecular weight of poly-(3-acrylamido phenyl boric acid) is 3000.
Embodiment 9: the preparation of hydroxypropyl cellulose-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
In the 25ml stirring reactor, be that 30 milligrams of hydroxypropyl celluloses of 30000 are dissolved in 8 ml distilled waters with 50 milligrams of 3-acrylamido phenyl boric acids and number-average molecular weight.Behind the cool to room temperature, add 4 milligram 4,4 '-azo (4-cyanopentanoic acid) initator.Be warmed up to 80 ℃, initiated polymerization 2 hours obtains the aqueous solution of hydroxypropyl cellulose-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.Stop reaction, system temperature is down to room temperature filters, dialysis is 24 hours in the bag filter (the Cut-off molecular weight is 100000) of after the filtration aqueous dispersions being packed into, removes unreacted monomer in the system.The average grain diameter of the Nano microsphere that records by dynamic light scattering is 84.5 ± 2.0nm, and wherein natural polymer accounts for 62%, and poly-(3-acrylamido phenyl boric acid) accounts for 38%.The number-average molecular weight of poly-(3-acrylamido phenyl boric acid) is 4000.
Embodiment 10: be loaded with the preparation of the glucan of adriamycin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
In the 10ml stirring reactor, get 5mL glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere and regulate pH value to 8.2 with NaOH, stir the lower 1mL ADMh aqueous solution (3mg/mL) that dropwise adds, drip off rear continuation and stirred 12 hours, obtain being loaded with the glucan of adriamycin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.The average grain diameter of the Nano microsphere that records by dynamic light scattering is 94.5 ± 2.0nm.Above-mentioned Nano microsphere is after centrifugal, and the concentration of the adriamycin in the supernatant solution is with the method mensuration of pass through calibration curve of fluorescence spectrum.The medicine carrying amount is 10%, and parcel efficient is 98%.
Embodiment 11: be loaded with the preparation of the glucan of adriamycin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
In the 10ml stirring reactor, get 5mL glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere and regulate pH value to 7.4 with NaOH, stir the lower 0.5mL ADMh aqueous solution (3mg/mL) that dropwise adds, drip off rear continuation and stirred 12 hours, obtain being loaded with the glucan of adriamycin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.The average grain diameter of the Nano microsphere that records by dynamic light scattering is 98.0 ± 2.0nm.Above-mentioned Nano microsphere is after centrifugal, and the concentration of the adriamycin in the supernatant solution is with the method mensuration of pass through calibration curve of fluorescence spectrum.The medicine carrying amount is 5%, and parcel efficient is 96%.
Embodiment 12: be loaded with the preparation of the bovine serum albumin of adriamycin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
In the 10ml stirring reactor, get 5mL bovine serum albumin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere and regulate pH value to 8.2 with NaOH, stir the lower 0.5mL ADMh aqueous solution (3mg/mL) that dropwise adds, drip off rear continuation and stirred 12 hours, obtain being loaded with the glucan of adriamycin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere.The average grain diameter of the Nano microsphere that records by dynamic light scattering is 42.0 ± 2.0nm..Above-mentioned Nano microsphere is after centrifugal, and the concentration of the adriamycin in the supernatant solution is with the method mensuration of pass through calibration curve of fluorescence spectrum.The medicine carrying amount is 5%, and parcel efficient is 95%.
Embodiment 13: the release in vitro that is loaded with the glucan of adriamycin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
Getting the glucan that the 1mL that makes among the embodiment 10 is loaded with adriamycin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere aqueous solution (amount of contained adriamycin is 0.5 milligram) is placed in the bag filter (the Cut-off molecular weight is 12000), then (pH 7.4 bag filter to be immersed fully 5mL 0.01mol/L PBS, pH 5.0, pH 4.0) in, under 37 ℃ of stirrings, carry out release experiment.Take out at regular intervals the 5mL dissolution medium, add again the new dissolution medium of 5mL.Content with adriamycin in the method working sample that passes through calibration curve of fluorescence spectrum.And according to cubage release percentage, the result can find out that the medicine that is carried on wherein shows continual and steady release characteristics under low pH value as shown in Figure 1.
Embodiment 14: the vitro cytotoxicity test of glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
Cell line is gastric carcinoma cells MKN-28.By the biotinylated biomolecule compatibility of the glucan among the mtt assay mensuration embodiment 1-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere, the time is 48h, the results are shown in Figure 2.As can be seen from Figure 2 glucan-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere does not have cytotoxicity, illustrates that this Nano microsphere is biocompatibility.
Embodiment 15: be loaded with the vitro cytotoxicity test of the glucan of adriamycin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere
Cell line is human cervical carcinoma cell Hela.By the external fragmentation effect of the glucan that is loaded with adriamycin among the mtt assay mensuration embodiment 1-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere to the Hela cell, the time is 48h, the results are shown in Figure 3.As can be seen from Figure 3 being loaded with the glucan of adriamycin-poly-(3-acrylamido phenyl boric acid) composite nano-microsphere does not have the ability of the naked medicine cell killing of adriamycin strong, good sustained drug release effect is arranged.
Claims (7)
1. a natural polymer-poly--3-acrylamido phenyl boric acid composite nano-microsphere, it is characterized in that: its surface is hydrophilic natural polymer, inside is hydrophobic gathering-3-acrylamido phenyl boric acid, the number-average molecular weight of natural polymer is in the 3000-100000 scope, content is the 5%-70% of composite nano-microsphere quality, the number-average molecular weight of poly--3-acrylamido phenyl boric acid is in the 2000-4000 scope, content is the 30%-95% of composite nano-microsphere quality, and the average grain diameter of Nano microsphere is the 40-100 nanometer.
2. natural polymer according to claim 1-poly--3-acrylamido phenyl boric acid composite nano-microsphere, it is characterized in that: described natural polymer can be glucan, shitosan, hydroxypropyl cellulose, alginic acid, heparin, bovine serum albumin.
3. a method for preparing natural polymer claimed in claim 1-poly--3-acrylamido phenyl boric acid composite nano-microsphere is characterized in that it comprises the steps:
Step 1. is under 40-80 ℃ of stirring, in distilled water, add natural polymer and 3-acrylamido phenyl boric acid, the mass ratio of natural polymer and 3-acrylamido phenyl boric acid is 0.5: 1～5: 1, and the total concentration of reactant is 5-30mg/ml in the system, and heating is stirred to fully dissolving;
After step 2. dissolve complete and the cooling, add radical initiator and regulate pH to 3-7 with NaOH, reaction is 1-4 hour under 60-90 ℃ of stirring, formation water nanoparticle dispersion liquid after reaction is finished.
4. the method for making of natural polymer according to claim 3-poly--3-acrylamido phenyl boric acid composite nano-microsphere, it is characterized in that: described initator is potassium peroxydisulfate or 4,4 '-azo (4-cyanopentanoic acid).
5. natural polymer claimed in claim 1-poly--3-acrylamido phenyl boric acid composite nano-microsphere is as the application in the pharmaceutical carrier.
6. the natural polymer that is loaded with ADMh-poly--3-acrylamido phenyl boric acid composite nano-microsphere, it is characterized in that: it be natural polymer claimed in claim 1-poly--3-acrylamido phenyl boric acid composite nano-microsphere as carrier, be loaded with the natural polymer that is loaded with ADMh-poly--3-acrylamido phenyl boric acid composite nano-microsphere of ADMh of the 5-10% of composite nano-microsphere quality.
7. method for preparing the natural polymer that is loaded with ADMh claimed in claim 6-poly--3-acrylamido phenyl boric acid composite nano-microsphere, it is characterized in that: it is that the aqueous dispersions of natural polymer claimed in claim 1-poly--3-acrylamido phenyl boric acid composite nano-microsphere is regulated pH behind 5-9 with NaOH, stir the lower ADMh that adds, the ratio of the amount of substance of phenyl boric acid unit is 0.1 in ADMh and the Nano microsphere: 1-1: 1, reaction is after 12-72 hour under stirring at room, dialysis, namely obtain being loaded with the natural polymer of ADMh-poly--3-acrylamido phenyl boric acid composite nano-microsphere, wherein, ADMh accounts for the 5-10% of composite nano-microsphere quality.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010213156XA CN101879427B (en) | 2010-06-29 | 2010-06-29 | Doxorubicin hydrochloride-carrying natural polymer-poly(3-benzene acid acrylamide) composite nanospheres, manufacturing method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010213156XA CN101879427B (en) | 2010-06-29 | 2010-06-29 | Doxorubicin hydrochloride-carrying natural polymer-poly(3-benzene acid acrylamide) composite nanospheres, manufacturing method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101879427A CN101879427A (en) | 2010-11-10 |
| CN101879427B true CN101879427B (en) | 2013-02-06 |
Family
ID=43051638
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010213156XA Active CN101879427B (en) | 2010-06-29 | 2010-06-29 | Doxorubicin hydrochloride-carrying natural polymer-poly(3-benzene acid acrylamide) composite nanospheres, manufacturing method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101879427B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104151339B (en) * | 2013-05-17 | 2017-05-03 | 中国科学院近代物理研究所 | Boron-containing acridine derivative as well as preparation method and application thereof |
| CN105616348A (en) * | 2016-03-08 | 2016-06-01 | 南通大学附属医院 | Novel adriamycin-loaded nanoscopic drug carrier of collagen-poly (3-acrylamide benzene boric acid) and preparation method of nanoscopic drug carrier |
| US10799587B2 (en) | 2016-05-11 | 2020-10-13 | Huan NIU | Ion implantation of neutron capture elements into nanodiamond particles to form composition for neutron capture therapy usage |
| CN106366182B (en) * | 2016-08-29 | 2019-10-18 | 四川大学 | PH response type magnetic composite nano ball and the preparation method and application thereof |
| CN108324954B (en) * | 2018-01-26 | 2020-10-27 | 西安交通大学 | Phenylboronic acid hyperbranched modified magnetic nanosphere and preparation method and application thereof |
| WO2020146691A1 (en) * | 2019-01-11 | 2020-07-16 | Encapsys, Llc | Incorporation of chitosan in microcapsule wall |
| CN113024316A (en) * | 2021-04-22 | 2021-06-25 | 唐满红 | Special biofertilizer for fruit trees and preparation method thereof |
| CN114525686A (en) * | 2021-07-14 | 2022-05-24 | 恒天嘉华非织造有限公司 | Auxiliary agent for manufacturing water-repellent cotton fibers and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1064912B1 (en) * | 1999-07-02 | 2004-01-28 | Cognis Iberia, S.L. | Microcapsules |
| CN1485094A (en) * | 2002-09-24 | 2004-03-31 | 中国科学院过程工程研究所 | Natural porous polymer beads, the preparation and application thereof |
| WO2009075652A1 (en) * | 2007-12-11 | 2009-06-18 | Nanyang Technological University | Hollow multi-layered microspheres for delivery of hydrophilic active compounds |
-
2010
- 2010-06-29 CN CN201010213156XA patent/CN101879427B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1064912B1 (en) * | 1999-07-02 | 2004-01-28 | Cognis Iberia, S.L. | Microcapsules |
| CN1485094A (en) * | 2002-09-24 | 2004-03-31 | 中国科学院过程工程研究所 | Natural porous polymer beads, the preparation and application thereof |
| WO2009075652A1 (en) * | 2007-12-11 | 2009-06-18 | Nanyang Technological University | Hollow multi-layered microspheres for delivery of hydrophilic active compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101879427A (en) | 2010-11-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101879427B (en) | Doxorubicin hydrochloride-carrying natural polymer-poly(3-benzene acid acrylamide) composite nanospheres, manufacturing method and application thereof | |
| Li et al. | Nanoscale metal‐organic frameworks: synthesis, biocompatibility, imaging applications, and thermal and dynamic therapy of tumors | |
| Xie et al. | O2-Cu/ZIF-8@ Ce6/ZIF-8@ F127 composite as a tumor microenvironment-responsive nanoplatform with enhanced photo-/chemodynamic antitumor efficacy | |
| Lei et al. | Constructing redox-responsive metal–organic framework nanocarriers for anticancer drug delivery | |
| Chen et al. | Drug‐loaded mesoporous tantalum oxide nanoparticles for enhanced synergetic chemoradiotherapy with reduced systemic toxicity | |
| Xiong et al. | Doxorubicin-loaded carborane-conjugated polymeric nanoparticles as delivery system for combination cancer therapy | |
| Wang et al. | Combination-responsive MoO3–x-hybridized hyaluronic acid hollow nanospheres for cancer phototheranostics | |
| CN107095859B (en) | Drug-loaded nanocapsule with tumor cell bioreductive microenvironment sensitivity and preparation method thereof | |
| CN110755385A (en) | Preparation method of zif-8 nanosphere loaded SERS (surface enhanced Raman Scattering) coded gold nanoparticles for intracellular photothermal therapy | |
| Moghaddam et al. | Fabrication of carboxymethyl chitosan nanoparticles to deliver paclitaxel for melanoma treatment | |
| CN102302503A (en) | Preparation method for daunorubicin and 5-bromotetrandrine co-carried magnetic ferrosoferric oxide nanoparticles | |
| EP2167097B1 (en) | Metal complexes incorporated within biodegradable nanoparticles and their use | |
| US20110064665A1 (en) | Diagnostic and therapeutic nanoparticles | |
| Ma et al. | Polyacrylic acid functionalized Co0. 85Se nanoparticles: An ultrasmall pH-responsive nanocarrier for synergistic photothermal-chemo treatment of cancer | |
| CN105997943A (en) | Nano-particles of human serum albumin loaded camptothecin drugs, as well as preparation method and application thereof | |
| CN108403641A (en) | A kind of medicament-carried nano material and preparation method thereof | |
| Liu et al. | Disulfide‐Bridged Dendritic Organosilicas‐Based Biodegradable Molecularly Imprinted Polymers for Multiple Targeting and pH/Redox‐Responsive Drug Release toward Chemical/Photodynamic Synergistic Tumor Therapy | |
| Yaray et al. | Chemoradiation therapy of 4T1 cancer cells with methotrexate conjugated platinum nanoparticles under X-Ray irradiation | |
| Hu et al. | Targeted transmembrane delivery of Ca2+ via FA-nanogel for synergistically enhanced chemotherapy | |
| CN114404604B (en) | Iodine-driven targeted identification intelligent response type magnetic nano drug delivery system and preparation method and application thereof | |
| CN105997942A (en) | Nano-particles of human serum albumin loaded maytansine medicines, as well as preparation method and application thereof | |
| CN105879051A (en) | Preparation and application of self-assembled nano-drug of core-shell structure | |
| CN112546236B (en) | PH-sensitive double-drug-skeleton polymer prodrug, and preparation method and application thereof | |
| CN104761732A (en) | Tumor cell targeted nano gel and preparation method thereof as well as tumor cell targeted drug-loaded nano-particles | |
| Colak et al. | Implantable, 3D-printed alginate scaffolds with bismuth sulfide nanoparticles for the treatment of local breast cancer via enhanced radiotherapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |