CN114470322B - 一种plga纳米载药纤维膜及其制备方法 - Google Patents
一种plga纳米载药纤维膜及其制备方法 Download PDFInfo
- Publication number
- CN114470322B CN114470322B CN202210020816.5A CN202210020816A CN114470322B CN 114470322 B CN114470322 B CN 114470322B CN 202210020816 A CN202210020816 A CN 202210020816A CN 114470322 B CN114470322 B CN 114470322B
- Authority
- CN
- China
- Prior art keywords
- solution
- plga
- drug
- lecithin
- loaded
- 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
- 229940079593 drug Drugs 0.000 title claims abstract description 63
- 239000003814 drug Substances 0.000 title claims abstract description 63
- 239000012528 membrane Substances 0.000 title claims abstract description 48
- 239000000835 fiber Substances 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 title claims 5
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims abstract description 65
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 43
- 229940067606 lecithin Drugs 0.000 claims abstract description 43
- 235000010445 lecithin Nutrition 0.000 claims abstract description 43
- 239000000787 lecithin Substances 0.000 claims abstract description 43
- 239000002121 nanofiber Substances 0.000 claims abstract description 38
- 102000008186 Collagen Human genes 0.000 claims abstract description 35
- 108010035532 Collagen Proteins 0.000 claims abstract description 35
- 229920001436 collagen Polymers 0.000 claims abstract description 35
- 238000009987 spinning Methods 0.000 claims abstract description 24
- 229920001577 copolymer Polymers 0.000 claims abstract description 18
- 229940009456 adriamycin Drugs 0.000 claims abstract description 16
- 238000010041 electrostatic spinning Methods 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 6
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 230000008569 process Effects 0.000 claims abstract description 4
- 238000003756 stirring Methods 0.000 claims abstract description 4
- 238000001523 electrospinning Methods 0.000 claims description 4
- 238000001291 vacuum drying Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 1
- 239000002994 raw material Substances 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 21
- 230000015556 catabolic process Effects 0.000 abstract description 4
- 239000002131 composite material Substances 0.000 abstract description 4
- 238000006731 degradation reaction Methods 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 abstract description 4
- 230000004048 modification Effects 0.000 abstract description 4
- 238000012986 modification Methods 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 52
- 239000000523 sample Substances 0.000 description 8
- 239000002344 surface layer Substances 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000002086 nanomaterial Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 210000001361 achilles tendon Anatomy 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000010586 diagram Methods 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
- 238000004090 dissolution Methods 0.000 description 1
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000002474 experimental method 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
- 230000007062 hydrolysis Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000013269 sustained drug release Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- 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
- D01F1/10—Other agents for modifying properties
-
- 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
- D01F6/00—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof
- D01F6/88—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from mixtures of polycondensation products as major constituent with other polymers or low-molecular-weight compounds
- D01F6/92—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from mixtures of polycondensation products as major constituent with other polymers or low-molecular-weight compounds of polyesters
-
- D—TEXTILES; PAPER
- D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
- D04H—MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
- D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
- D04H1/40—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties
- D04H1/42—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties characterised by the use of certain kinds of fibres insofar as this use has no preponderant influence on the consolidation of the fleece
- D04H1/4326—Condensation or reaction polymers
-
- D—TEXTILES; PAPER
- D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
- D04H—MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
- D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
- D04H1/70—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
- D04H1/72—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
- D04H1/728—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/23—Carbohydrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Textile Engineering (AREA)
- Transplantation (AREA)
- General Chemical & Material Sciences (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Manufacturing & Machinery (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种PLGA纳米载药纤维膜及其制备方法，包括，以六氟异丙醇作为溶剂，分别配制聚乳酸‑羟基乙酸共聚物溶液、胶原蛋白溶液、卵磷脂溶液和阿霉素溶液；将聚乳酸‑羟基乙酸共聚物溶液、胶原蛋白溶液、卵磷脂溶液和阿霉素溶液进行混合，充分搅拌均匀后，得到混合纺丝液；将混合纺丝液通过静电纺丝工艺，制得PLGA纳米载药纤维膜。本发明为改善聚乳酸‑羟基乙酸共聚物(PLGA)降解速率缓慢的问题，并提高PLGA载药材料的持续释药性能，借助静电纺丝技术，采用胶原蛋白(Col)和卵磷脂(lecithin)对PLGA复合改性与阿霉素(DOX)载药处理的方式制备得到PLGA/Col/lecithin/DOX纳米纤维，可作为载药组织工程支架材料使用。
Description
技术领域
本发明属于纳米纤维制备技术领域，具体涉及到一种PLGA纳米载药纤维膜及其制备方法。
背景技术
聚乳酸-羟基乙酸共聚物(PLGA)，是一种环保绿色材料，具有良好的生物相容性和体内降解性。PLGA在体内可以通过水解作用完全分解为二氧化碳和水，并可通过新陈代谢排出体外。同时，PLGA具有非常好的成膜、成囊和成纤性能。因此，PLGA作为高分子材料被广泛用于药物载体材料、外科缝合线和医用组织工程材料等领域。
PLGA虽然在很多应用中具有优异的性能，但由于其较强的疏水性，在作为药物传递系统应用的过程中存在药物释放速率太慢、药物释放量过低的问题。尤其作为组织工程支架材料应用时，由于降解速率缓慢，多数在体内降解周期可达六个月以上，长期留存于体内对身体产生潜在组织炎症和机体排异等副作用。
发明内容
本部分的目的在于概述本发明的实施例的一些方面以及简要介绍一些较佳实施例。在本部分以及本申请的说明书摘要和发明名称中可能会做些简化或省略以避免使本部分、说明书摘要和发明名称的目的模糊，而这种简化或省略不能用于限制本发明的范围。
鉴于上述和/或现有技术中存在的问题，提出了本发明。
因此，本发明的目的是，克服现有技术中的不足，提供一种PLGA纳米载药纤维膜的制备方法。
为解决上述技术问题，本发明提供了如下技术方案：一种PLGA纳米载药纤维膜的制备方法，包括，
以六氟异丙醇作为溶剂，分别配制聚乳酸-羟基乙酸共聚物溶液、胶原蛋白溶液、卵磷脂溶液和阿霉素溶液；
将聚乳酸-羟基乙酸共聚物溶液、胶原蛋白溶液、卵磷脂溶液和阿霉素溶液进行混合，充分搅拌均匀后，得到混合纺丝液；
将混合纺丝液通过静电纺丝工艺，制得PLGA纳米载药纤维膜。
作为本发明所述PLGA纳米载药纤维膜的制备方法的一种优选方案，其中：所述聚乳酸-羟基乙酸共聚物溶液、胶原蛋白溶液、卵磷脂溶液和阿霉素溶液的浓度分别为0.05～0.1g/mL、0.05～0.1g/mL、0.05～0.1g/mL和0.01～0.02g/mL。
作为本发明所述PLGA纳米载药纤维膜的制备方法的一种优选方案，其中：所述聚乳酸-羟基乙酸共聚物溶液、胶原蛋白溶液、卵磷脂溶液和阿霉素溶液的浓度分别为0.1g/mL、0.1g/mL、0.1g/mL和0.01g/mL。
作为本发明所述PLGA纳米载药纤维膜的制备方法的一种优选方案，其中：所述将聚乳酸-羟基乙酸共聚物溶液、胶原蛋白溶液、卵磷脂溶液和阿霉素溶液进行混合，其中，聚乳酸-羟基乙酸共聚物溶液、胶原蛋白溶液和阿霉素溶液的体积比为6～10:0～4:0～4:0～1。
作为本发明所述PLGA纳米载药纤维膜的制备方法的一种优选方案，其中：聚乳酸-羟基乙酸共聚物溶液、胶原蛋白溶液、卵磷脂溶液和阿霉素溶液的体积比为10:2:2:1。
作为本发明所述PLGA纳米载药纤维膜的制备方法的一种优选方案，其中：静电纺丝，其中，纺丝条件：环境温度为25℃左右，环境湿度为45％，电源电压为18kV，喷丝头与接收板距离为15cm，溶液流速为1.2mL/h，纺丝时间为1h。
作为本发明所述PLGA纳米载药纤维膜的制备方法的一种优选方案，其中：纺丝结束后，将纳米纤维膜放入真空干燥箱烘干，去除溶剂。
本发明的再一个目的是，克服现有技术中的不足，提供一种PLGA纳米载药纤维膜的制备方法制得的纳米载药纤维膜，纳米载药纤维膜的接触角为0°，亲水性佳；纳米载药纤维膜的药物释放速率高。
本发明有益效果：
(1)本发明为改善聚乳酸-羟基乙酸共聚物(PLGA)降解速率缓慢的问题，并提高PLGA载药材料的持续释药性能，借助静电纺丝技术，采用胶原蛋白(Col)和卵磷脂(lecithin)对PLGA复合改性与阿霉素(DOX)载药处理的方式制备得到PLGA/Col/lecithin/DOX纳米纤维，可作为载药组织工程支架材料使用。
(2)本发明PLGA/Col/lecithin/DOX纳米纤维，体外药物释放实验表明，经胶原蛋白和卵磷脂改性后的载药纳米纤维的药物释放速率明显提高，能够有效改善PLGA释药速率和释药量过低的问题，提高了药物利用率。
(3)本发明将聚乳酸-羟基乙酸共聚物经过胶原蛋白溶液、卵磷脂溶液改性协同作用，制得的纳米纤维膜材料的接触角测量结果为0°，胶原蛋白和卵磷脂的同时载入能够促进纳米纤维膜材料界面亲水性的巨大改善，实现了纳米结构表面材料疏水与亲水之间的单向转变。
附图说明
为了更清楚地说明本发明实施例的技术方案，下面将对实施例描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动性的前提下，还可以根据这些附图获得其它的附图。其中：
图1为本发明实施例中PLGA(a)和PLGA/Col/lecithin/DOX(b)纳米纤维的扫描电镜图(×20000)。
图2为本发明实施例中纯PLGA(a)和PLGA/Col/lecithin/DOX(b)纳米纤维膜的接触角图。
图3为本发明实施例中PLGA/DOX、PLGA/Col/DOX和PLGA/Col/lecithin/DOX载药纳米纤维膜的药物释放对比图。
具体实施方式
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合说明书实施例对本发明的具体实施方式做详细的说明。
在下面的描述中阐述了很多具体细节以便于充分理解本发明，但是本发明还可以采用其他不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似推广，因此本发明不受下面公开的具体实施例的限制。
其次，此处所称的“一个实施例”或“实施例”是指可包含于本发明至少一个实现方式中的特定特征、结构或特性。在本说明书中不同地方出现的“在一个实施例中”并非均指同一个实施例，也不是单独的或选择性的与其他实施例互相排斥的实施例。
本发明中材料与仪器：
聚乳酸-羟基乙酸75/25(PLGA)(Mw＝12～16万，济南岱罡生物工程有限公司)；牛跟腱I型胶原蛋白(Col)、盐酸阿霉素(DOX·HCl，98％)、六氟异丙醇(99.5％)(上海麦克林生化科技有限公司)；磷酸缓冲盐溶液(PBS，pH＝7.4)(南京森贝伽生物科技有限公司)；
DP30-S型静电纺丝机(天津云帆科技有限公司)；JCY-2型接触角测试仪(上海轩准仪器有限公司)；BX-51型光学显微镜(奥林巴斯有限公司)；UV1810S型紫外分光光度计(上海精科实业有限公司)；WHY-2型恒温水浴振荡锅(上海达姆实业有限公司)。
本发明测试与表征方法：
纤维形貌表征：
扫描电镜观察。对纳米纤维膜喷金处理后，利用Nova NanoSEM 450型场发射扫描电子显微镜(美国FEI公司)观察纳米纤维的形貌。
接触角测试：
将纳米纤维膜的待测样品连同锡箔纸一同裁剪成20mm×20mm的试样尺寸，平铺固定并放置在JCY-2型接触角测试仪(上海轩准仪器有限公司)工作台上进行测试并读数。液滴为去离子水，液滴体积为3μL，每个样品测量3次求平均值。
载药纳米纤维膜体外药物释放速率测试：
使用电子分析天平精确称量载药纳米纤维膜各25mg并置于50mL离心管中，随后注入25mL、pH＝7.4的PBS缓冲溶液，每个样品设置3份平行样。
将离心管密封后置于恒温摇床中，设置温度为37℃，摇床速度为100r/min。在适当的时间间隔量取2mL溶液待测，同时向原样中补充5mL新鲜PBS溶液，保持离心管中的液体体积不变。
使用UV1810S型紫外-可见分光光度计(上海精科实业有限公司)将取出的样品溶液在DOX最大吸收波长波长480.0nm处测试其吸光度A，并通过标准曲线(标准曲线A＝12.079C+0.1517。其中A为DOX溶液的吸光度值；C为DOX溶液的浓度，单位为g/L。)计算出样品溶液中药的浓度C，进一步计算其累积释放量。
实施例1
本实施例提供一种PLGA纳米载药纤维膜的制备方法，主要步骤为：
(1)DOX、PLGA、Col和lecithin溶液的制备
以六氟异丙醇作为DOX、PLGA、Col和lecithin的溶剂，分别配制浓度为0.1g/mLPLGA溶液、0.1g/mL胶原蛋白溶液、0.1g/mL卵磷脂溶液和0.01g/mL DOX溶液。
(2)PLGA、胶原蛋白溶液的复配
按照表1所示不同组分的体积比进行纺丝液的混合，待充分搅拌均匀后，分别得到PLGA、PLGA/collagen、PLGA/lecithin和PLGA/Col/lecithin/DOX纺丝液，于纺丝前分别转移至注射器中，备用。
表1纺丝液的复配组分
| PLGA/mL | collagen/mL | lecithin/mL | DOX/mL | |
| PLGA | 10 | 0 | 0 | 0 |
| PLGA/collagen | 10 | 4 | 0 | 0 |
| PLGA/lecithin | 10 | 0 | 4 | 0 |
| PLGA/Col/lecithin/DOX | 10 | 2 | 2 | 1 |
(3)静电纺丝工艺的条件控制
DP30-S型静电纺丝机(天津云帆科技有限公司)纺丝条件：环境温度为25℃，环境湿度为45％，电源电压为18kV，喷丝头与接收板距离为15cm，溶液流速为1.2mL/h，每一个样品设置三个平行样，每个平行样的纺丝时间为1h。
纺丝结束后，关闭所有电源开关并将电压恢复至零，然后取下铝箔纸，并将这些覆有纳米纤维膜的铝箔纸放入真空干燥箱烘干48h以去除残余溶剂，制得纤维膜。
实施例2
将实施例1制得的PLGA纤维、PLGA/Col/lecithin/DOX纤维，进行纳米纤维的形貌表征。
图1采用场发射扫描电镜观察纳米纤维的形貌；可见，PLGA、PLGA/Col/lecithin/DOX两种纳米纤维的直径为250～500nm，呈现出变细的趋势。
实施例3
将实施例1制得的纳米纤维膜进行亲疏水性分析。
图2是实施例1中PLGA和PLGA/Col/lecithin/DOX制得的纳米纤维膜接触角测量图，表2为不同纳米纤维膜的接触角。
表2
可以看出，PLGA纳米纤维膜的接触角为93.5°，显示疏水性；PLGA/胶原蛋白复合纳米纤维膜、载有lecithin的PLGA纳米纤维膜的接触角均将至50°左右，说明胶原蛋白或lecithin的载入能够使得PLGA膜材料的固体界面上呈现出一定程度的亲水性。
PLGA/Col/lecithin三者共混纳米纤维膜材料的接触角测量结果为0°，该结果进一步说明，胶原蛋白和lecithin的同时载入能够促进纳米纤维膜材料界面亲水性的巨大改善，实现了纳米结构表面材料疏水与亲水之间的单向转变。
其中一方面与胶原蛋白上的极性基团有关，处于纤维表层的卵磷脂由于具有亲水基，能够进一步增加纤维表层的亲水性；而纤维膜的亲水性越好，水分子越容易进入聚合物内部，从而促进PLGA高聚物发生水解反应，同时有助于提高纳米纤维载药体系的释药性。
实施例4
体外释药性能测定：
PLGA/DOX、PLGA/collagen/DOX和PLGA/Col/lecithin/DOX结果见表3。
表3
| PLGA/mL | collagen/mL | lecithin/mL | DOX/mL | |
| PLGA/DOX | 10 | 0 | 0 | 1 |
| PLGA/collagen/DOX | 10 | 4 | 0 | 1 |
| PLGA/Col/lecithin/DOX | 10 | 2 | 2 | 1 |
体外释药性能测定结果见图3，可以看出，添加亲水性的胶原蛋白和双亲性的卵磷脂具有协同作用：卵磷脂在混合纺丝液喷出的时候，在静电作用下发生重组，处于纤维内部的卵磷脂更加容易形成空腔结构，促进药物分子储存和溶出，处于纤维表层的卵磷脂由于具有亲水基，能够进一步增加纤维表层的亲水性，结合胶原蛋白上的极性基团作用，经胶原蛋白和卵磷脂改性后的载药纳米纤维的药物释放速率明显提高，能够有效改善PLGA释药速率和释药量过低的问题，提高物利用率。
本发明为改善聚乳酸-羟基乙酸共聚物(PLGA)降解速率缓慢的问题，并提高PLGA载药材料的持续释药性能，借助静电纺丝技术，采用胶原蛋白(Col)对PLGA复合改性与阿霉素(DOX)载药处理的方式制备得到PLGA/Col/DOX纳米纤维，可作为载药组织工程支架材料使用。
应说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的精神和范围，其均应涵盖在本发明的权利要求范围当中。
Claims (3)
1.一种PLGA纳米载药纤维膜的制备方法，其特征在于：包括，
以六氟异丙醇作为溶剂，分别配制聚乳酸-羟基乙酸共聚物溶液、胶原蛋白溶液、卵磷脂溶液和阿霉素溶液；
将聚乳酸-羟基乙酸共聚物溶液、胶原蛋白溶液、卵磷脂溶液和阿霉素溶液进行混合，充分搅拌均匀后，得到混合纺丝液；
将混合纺丝液通过静电纺丝工艺，制得PLGA纳米载药纤维膜；其中，
所述聚乳酸-羟基乙酸共聚物溶液、胶原蛋白溶液、卵磷脂溶液和阿霉素溶液的浓度分别为0.1g/mL、0.1g/mL、0.1g/mL和0.01g/mL；
聚乳酸-羟基乙酸共聚物溶液、胶原蛋白溶液、卵磷脂溶液和阿霉素溶液的体积比为10:2:2:1；
静电纺丝，其中，纺丝条件：环境温度为25℃，环境湿度为45%，电源电压为18 kV，喷丝头与接收板距离为15 cm，溶液流速为1.2 mL/ h，纺丝时间为1 h；
纳米载药纤维膜的接触角为0°，亲水性佳，纳米载药纤维膜的药物释放速率高。
2.如权利要求1所述的PLGA纳米载药纤维膜的制备方法，其特征在于：纺丝结束后，将纳米纤维膜放入真空干燥箱烘干，去除溶剂。
3.权利要求1或2所述的PLGA纳米载药纤维膜的制备方法制得的纳米载药纤维膜。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210020816.5A CN114470322B (zh) | 2022-01-10 | 2022-01-10 | 一种plga纳米载药纤维膜及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210020816.5A CN114470322B (zh) | 2022-01-10 | 2022-01-10 | 一种plga纳米载药纤维膜及其制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114470322A CN114470322A (zh) | 2022-05-13 |
| CN114470322B true CN114470322B (zh) | 2022-12-23 |
Family
ID=81509731
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210020816.5A Active CN114470322B (zh) | 2022-01-10 | 2022-01-10 | 一种plga纳米载药纤维膜及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114470322B (zh) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101219238A (zh) * | 2007-01-11 | 2008-07-16 | 北京奥精医药科技有限公司 | 复合生物可降解合成高分子材料 |
| CN103572508A (zh) * | 2012-07-26 | 2014-02-12 | 中国科学院理化技术研究所 | 乳液电纺法制备可生物降解聚合物纳米纤维膜 |
| CN106757790A (zh) * | 2017-01-17 | 2017-05-31 | 国家纳米科学中心 | 一种抗氧化静电纺丝膜及其制备方法和应用 |
| CN109898236A (zh) * | 2019-03-15 | 2019-06-18 | 深圳市光远生物材料有限责任公司 | 一种载药纳米纤维膜及其制备方法和应用 |
| CN111979593A (zh) * | 2019-05-21 | 2020-11-24 | 财团法人纺织产业综合研究所 | 聚乳酸复合纤维及其制备方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101172164A (zh) * | 2006-11-03 | 2008-05-07 | 中国科学院化学研究所 | 可生物降解及吸收的生物高分子纳米纤维膜材料及其制法和用途 |
| CN102908665B (zh) * | 2012-10-26 | 2014-12-10 | 东华大学 | 用串珠纤维担载蛋白颗粒的组织工程纤维支架的制备方法 |
| CN107675364B (zh) * | 2017-10-18 | 2020-04-24 | 天津工业大学 | 以乳液电纺技术制备双载药复合纤维膜的方法 |
-
2022
- 2022-01-10 CN CN202210020816.5A patent/CN114470322B/zh active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101219238A (zh) * | 2007-01-11 | 2008-07-16 | 北京奥精医药科技有限公司 | 复合生物可降解合成高分子材料 |
| CN103572508A (zh) * | 2012-07-26 | 2014-02-12 | 中国科学院理化技术研究所 | 乳液电纺法制备可生物降解聚合物纳米纤维膜 |
| CN106757790A (zh) * | 2017-01-17 | 2017-05-31 | 国家纳米科学中心 | 一种抗氧化静电纺丝膜及其制备方法和应用 |
| CN109898236A (zh) * | 2019-03-15 | 2019-06-18 | 深圳市光远生物材料有限责任公司 | 一种载药纳米纤维膜及其制备方法和应用 |
| CN111979593A (zh) * | 2019-05-21 | 2020-11-24 | 财团法人纺织产业综合研究所 | 聚乳酸复合纤维及其制备方法 |
Non-Patent Citations (2)
| Title |
|---|
| 《Nanofibrous rhPDGF-eluting PLGA–collagen hybrid scaffolds enhance healing of diabetic wounds》;Lee, CH et al.;《RSC Advances》;20161231;第6卷(第8期);第6276-6284页 * |
| 《Soybean-derived phospholipids complexed poly (lactic-co-glycolic acid) nanofibrous scaffolds for tissue engineering applications.》;Mao Ying et al.;《Materials & Design》;20210731;第205卷;第1-9页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114470322A (zh) | 2022-05-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yang et al. | Biomimetic composite scaffolds based on surface modification of polydopamine on electrospun poly (lactic acid)/cellulose nanofibrils | |
| Das et al. | Surface modification of electrospun PVA/chitosan nanofibers by dielectric barrier discharge plasma at atmospheric pressure and studies of their mechanical properties and biocompatibility | |
| Rinoldi et al. | Nanobead-on-string composites for tendon tissue engineering | |
| Unal et al. | Glioblastoma cell adhesion properties through bacterial cellulose nanocrystals in polycaprolactone/gelatin electrospun nanofibers | |
| Ali et al. | Dual nanofiber scaffolds composed of polyurethane-gelatin/nylon 6-gelatin for bone tissue engineering | |
| Zhou et al. | Electrospun scaffolds of silk fibroin and poly (lactide-co-glycolide) for endothelial cell growth | |
| Wang et al. | Fabrication and characterization of electrospun gelatin-heparin nanofibers as vascular tissue engineering | |
| Liang et al. | Synthesis of cellulose diacetate based copolymer electrospun nanofibers for tissues scaffold | |
| Zhou et al. | Evaluation of the potential of chimeric spidroins/poly (L-lactic-co-ε-caprolactone)(PLCL) nanofibrous scaffolds for tissue engineering | |
| Mao et al. | Soybean-derived phospholipids complexed poly (lactic-co-glycolic acid) nanofibrous scaffolds for tissue engineering applications | |
| Wei et al. | A novel approach for efficient fabrication of chitosan nanoparticles-embedded bacterial nanocellulose conduits | |
| CN111850731A (zh) | 醇溶蛋白基核壳纤维膜及食品贮藏保鲜材料和制备方法 | |
| Sanz-Horta et al. | Breath figures makes porous the “so-called” skin layer obtained in polymer foams prepared by supercritical CO2 treatments | |
| Lai et al. | Comparative evaluation of the biocompatible and physical–chemical properties of poly (lactide-co-glycolide) and polydopamine as coating materials for bacterial cellulose | |
| CN113046917B (zh) | 一种静电纺丝胶原膜及其制备方法 | |
| Xu et al. | Highly antibacterial electrospun double-layer mats for preventing secondary wound damage and promoting unidirectional water conduction in wound dressings | |
| CN114470322B (zh) | 一种plga纳米载药纤维膜及其制备方法 | |
| CN109999222B (zh) | 基于聚羟基脂肪酸酯/海藻酸钠电纺纳米纤维的神经导管材料的制备方法 | |
| CN109943974B (zh) | 基于聚羟基脂肪酸酯/明胶电纺纳米纤维的神经导管材料的制备方法 | |
| Fan et al. | A Transparent Additive‐Free Fibrous Facial Mask for Skin Moisturizing | |
| Jasim et al. | Improving the mechanical properties of (chitosan/polyurethane) electrospun blend scaffold used for skin regeneration | |
| CN111388739A (zh) | 一种纳米二氧化硅/分解酶/聚己内酯复合微球及其制备方法和应用 | |
| Chen et al. | Characterization on modification and biocompatibility of PCL scaffold prepared with near-field direct-writing melt electrospinning | |
| CN111455498A (zh) | 一种纳米纤维的制备方法和用途 | |
| CN115068687A (zh) | 梯度纳/微纤维支架及其制备方法与应用 |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20220513 Assignee: DONGTAI GAOKE TECHNOLOGY INNOVATION PARK Co.,Ltd. Assignor: YANCHENG INSTITUTE OF TECHNOLOGY Contract record no.: X2024980001259 Denomination of invention: A PLGA nano drug loaded fiber membrane and its preparation method Granted publication date: 20221223 License type: Common License Record date: 20240123 |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20240926 Address after: No. 2-302, Central Shanshui, Nangang Road, Majiadian Street, Zhijiang City, Yichang City, Hubei Province, China 443299 Patentee after: Hubei Chunshuo Technology Partnership Enterprise (Limited Partnership) Country or region after: China Address before: 224051 No. 1 hope road middle road, Ting Hu District, Yancheng City, Jiangsu Patentee before: YANCHENG INSTITUTE OF TECHNOLOGY Country or region before: China |