CN105543998A - 一种负载抗肿瘤药物的有序纳米纤维及其制备方法 - Google Patents

一种负载抗肿瘤药物的有序纳米纤维及其制备方法 Download PDF

Info

Publication number
CN105543998A
CN105543998A CN201510915089.9A CN201510915089A CN105543998A CN 105543998 A CN105543998 A CN 105543998A CN 201510915089 A CN201510915089 A CN 201510915089A CN 105543998 A CN105543998 A CN 105543998A
Authority
CN
China
Prior art keywords
antineoplastic
fibers
load
preparation
ordered nano
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.)
Granted
Application number
CN201510915089.9A
Other languages
English (en)
Other versions
CN105543998B (zh
Inventor
汤须崇
寇馨月
雷廷平
肖尚晨
徐祥
赵雯
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Huaqiao University
Original Assignee
Huaqiao University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Huaqiao University filed Critical Huaqiao University
Priority to CN201510915089.9A priority Critical patent/CN105543998B/zh
Publication of CN105543998A publication Critical patent/CN105543998A/zh
Application granted granted Critical
Publication of CN105543998B publication Critical patent/CN105543998B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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
    • 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
    • A61L27/222—Gelatin
    • 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
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • 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
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0015—Electro-spinning characterised by the initial state of the material
    • D01D5/003—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
    • D01D5/0076—Electro-spinning characterised by the electro-spinning apparatus characterised by the collecting device, e.g. drum, wheel, endless belt, plate or grid
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
    • D01D5/0092—Electro-spinning characterised by the electro-spinning apparatus characterised by the electrical field, e.g. combined with a magnetic fields, using biased or alternating fields
    • 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
    • D01F4/00—Monocomponent artificial filaments or the like of proteins; Manufacture thereof
    • 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
    • D04H1/4266—Natural fibres not provided for in group D04H1/425
    • 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
    • D04H1/435—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
    • D04H1/70—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
    • A61L2300/40—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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Textile Engineering (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • Transplantation (AREA)
  • General Chemical & Material Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biomedical Technology (AREA)
  • Manufacturing & Machinery (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Inorganic Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

本发明公开了一种负载抗肿瘤药物的有序纳米纤维及其制备方法，实现了有序纳米纤维的制备，得到的纤维直径小，力学性能良好，负载的药物浓度分布均匀，可实现良好的缓控释效果，且制备方法简单快捷，成本低，绿色环保，重复性好，适用于工业化生产。

Description

一种负载抗肿瘤药物的有序纳米纤维及其制备方法
技术领域
本发明涉及一种负载抗肿瘤药物的有序纳米纤维及其制备方法。
背景技术
随着纳米技术的不断发展，由静电纺丝技术制备纳米纤维在生物医药领域得到广泛研究和应用。经电纺制得的纳米纤维具有比表面积大，孔隙率高以及抗拉性能良好等结构特性。高分子材料可降解且制得的纳米纤维孔隙率较高，载药纳米纤维膜可以在体内缓慢释放，根据高分子聚合物降解速度控制药物在体内的释放时间，达到缓释效果，且体内无突释现象。电纺纳米纤维载药为缓释制剂的开发提供了新的思路，有望在生物医药领域得到广泛应用。
聚己内酯(PCL)、聚乳酸(PLGA)、明胶(Gelatin)、丝素(Fibroin)等高分子聚合物在体内均具有良好的相容性、降解性，在体外溶解性好。以聚己内酯为例，细胞可在其基架上正常生长，在体内6～12月可完全降解为CO2和H2O，其在芳香化合物、酮类和极性溶剂中可以很好地溶解，因此PCL作为药物载体在静电纺丝已经得到了广泛应用。
目前静电纺丝的接收工艺以无序接收为主，无序接收简便、快捷，适合于批量生产。但存在的问题也不容忽略，无序的排列可能导致局部药物分布不均匀，极有可能出现药物突释现象，不但缓释效果受到影响，还可能导致局部血药浓度过高，对人体产生危害。
发明内容
本发明的目的在于克服现有技术的不足之处，提供了一种负载抗肿瘤药物的有序纳米纤维及其制备方法，实现了有序纳米纤维的制备，直径小，力学性能良好，负载的药物浓度分布均匀，可实现良好的缓控释效果。
本发明解决其技术问题所采用的技术方案之一是：
一种负载抗肿瘤药物的有序纳米纤维的制备方法，包括：
1)按质量份数计，将6～9份第一溶剂和1～4份第二溶剂混合配制得到混合溶剂；将分子量为8×103～9×104Da的聚己内酯和抗肿瘤药物溶于该混合溶剂中，其中抗肿瘤药物的质量不超过抗肿瘤药物与聚己内酯的总质量的35％，且溶解后聚己内酯的终浓度为9～15％，25～30℃下搅拌12～24h，静置脱泡2～8h，得到静电纺丝溶液；
2)在25～35℃，相对湿度40～70％条件下将步骤1)的静电纺丝溶液进行电纺，纺丝电压为3～14kV，纺丝流速为100～1200μL/h；接收器为上下平行间隔布置的平行板接收器，且两板间距为1～100cm；喷丝口与接收器的水平距离为10～25cm；在接收器上即可得到所述之负载抗肿瘤药物的有序纳米纤维，干燥后形成有序纳米纤维膜，纤维平均直径为530～820nm，抗肿瘤药物的负载量不大于35％。
一实施例中：所述抗肿瘤药物的质量占抗肿瘤药物与聚己内酯的总质量的1～30％；所述抗肿瘤药物的负载量为1～30％。
一实施例中：所述抗肿瘤药物为紫杉醇、多烯紫杉醇、喜树碱、依托泊苷、甲氨蝶呤中的至少一种，且药物纯度不低于95％。
一实施例中：所述第一溶剂为二氯甲烷、三氯甲烷、三氟乙醇、六氟异丙醇中的一种。
一实施例中：所述第二溶剂为二甲基甲酰胺、二甲亚砜、甲醇、乙腈中的一种。
一实施例中：所述聚己内酯用聚乳酸、丝素、明胶中的一种替代。
一实施例中：还包括：得到所述之负载抗肿瘤药物的有序纳米纤维后，在垂直于纤维排列的方向上重复电纺步骤，干燥，得到纤维相互交织的有序纳米纤维膜。
本发明解决其技术问题所采用的技术方案之二是：
根据上述的制备方法制备的负载抗肿瘤药物的有序纳米纤维在制备抗肿瘤药物中的应用，包括制备抗肿瘤药物的剂型。
本发明解决其技术问题所采用的技术方案之三是：
一种负载抗肿瘤药物的有序纳米纤维，所述纤维有序排列，纤维平均直径为530～820nm，抗肿瘤药物的负载量不大于30％。
本技术方案与背景技术相比，它具有如下优点：
1.本发明的负载抗肿瘤药物的有序纳米纤维由静电纺丝方法制成，具有比表面积大，孔隙率高，安全可降解特性，可广泛用于药物缓控释制剂，神经组织工程支架等领域。
2.本发明的负载抗肿瘤药物的有序纳米纤维载药浓度分布均匀，有效的解决了无序纤维载药过程中载药量局部差异较大的问题，且纤维在体内降解速率稳定，从而保证药物在体内持续、均匀释放，实现良好的缓控释效果。
3..本发明提供了不同载药浓度下纳米纤维的特性及体内药物释放情况，可以根据不同场合下的拉力强度要求，判断合理的载药浓度范围，更可以根据病人自身情况不同而改变用药浓度及用药量，为个性化给药提供了思路，治疗效果更加理想。
4.本发明的制备方法操作简单，成本低，对环境友好，经济效益高。
附图说明
下面结合附图和实施例对本发明作进一步说明。
图1为本发明各实施例采用的静电纺丝装置示意图。
图2a为本发明实施例1的有序PCL/紫杉醇纳米纤维的扫描电镜照片，放大倍数为1000倍。
图2b为传统无序接收法制得的PCL/紫杉醇纳米纤维扫描电镜照片，放大倍数为11000倍。
图3为实施例3、实施例4和对比例的有序PCL/紫杉醇纳米纤维膜应力-应变曲线，图中横坐标Displacement为应变(单位为mm)，图中纵坐标TensileStress为应力(单位为MPa)。
图4为实施例3、实施例4的有序PCL/紫杉醇纳米纤维膜释放曲线。
具体实施方式
下面通过实施例具体说明本发明的内容：
实施例1
1)按质量份数计，将8份二氯甲烷和2份二甲基甲酰胺混合配制得到混合溶剂；将分子量为8×104Da的聚己内酯(PCL)和抗肿瘤药物紫杉醇(纯度≥95％)溶于该混合溶剂中，其中紫杉醇的量占紫杉醇与聚己内酯的总质量的1％，且溶解后聚己内酯的终浓度为10％；25℃下搅拌12h，静置脱泡2h，得到静电纺丝溶液；
2)在25～35℃，相对湿度40～70％条件下将步骤1)的静电纺丝溶液放入注射器中，进行电纺，纺丝电压为8kV，纺丝流速为600μL/h；接收器为上下平行间隔布置的平行板接收器，且两板间距为10cm；注射器针头即喷丝口与接收器的水平距离为12cm；接收60min后在接收器上即可得到有序PCL/紫杉醇纳米纤维，置于真空干燥箱内以室温干燥12～24h待其溶剂完全蒸发后形成有序PCL/紫杉醇纳米纤维膜，紫杉醇负载量为1％。
扫描电镜(SEM)观察纤维平行排列度高，如图2a所示，纤维平均直径为530nm。
实施例2
1)按质量份数计，将8份二氯甲烷和2份二甲基甲酰胺混合配制得到混合溶剂；将分子量为8×104Da的聚己内酯和抗肿瘤药物紫杉醇(纯度≥95％)溶于该混合溶剂中，其中紫杉醇的量占紫杉醇与聚己内酯的总质量的2％，且溶解后聚己内酯的终浓度为10％，25℃下搅拌12h，静置脱泡2h，得到静电纺丝溶液；
2)在25～35℃，相对湿度40～70％条件下将步骤1)的静电纺丝溶液放入注射器中，进行电纺，纺丝电压为8kV，纺丝流速为600μL/h；接收器为上下平行间隔布置的平行板接收器，且两板间距为10cm；注射器针头即喷丝口与接收器的水平距离为12cm；接收60min后在接收器上即可得到有序PCL/紫杉醇纳米纤维，置于真空干燥箱内以室温干燥12～24h待其溶剂完全蒸发后形成有序PCL/紫杉醇纳米纤维膜，紫杉醇负载量为2％。
扫描电镜(SEM)观察纤维平行排列度高，纤维平均直径为640nm。
实施例3
1)按质量份数计，将8份二氯甲烷和2份二甲基甲酰胺混合配制得到混合溶剂；将分子量为8×104Da的聚己内酯和抗肿瘤药物紫杉醇(纯度≥95％)溶于该混合溶剂中，其中紫杉醇的量占紫杉醇与聚己内酯的总质量的3％，且溶解后聚己内酯的终浓度为10％，25℃下搅拌12h，静置脱泡2h，得到静电纺丝溶液；
2)在25～35℃，相对湿度40～70％条件下将步骤1)的静电纺丝溶液放入注射器中，进行电纺，纺丝电压为8kV，纺丝流速为600μL/h；接收器为上下平行间隔布置的平行板接收器，且两板间距为10cm；注射器针头即喷丝口与接收器的水平距离为12cm；接收60min后在接收器上即可得到有序PCL/紫杉醇纳米纤维，置于真空干燥箱内以室温干燥12～24h待其溶剂完全蒸发后形成有序PCL/紫杉醇纳米纤维膜，紫杉醇负载量为3％。
扫描电镜(SEM)观察纤维平行排列度高，纤维平均直径为750nm。
实施例4
1)按质量份数计，将8份二氯甲烷和2份二甲基甲酰胺混合配制得到混合溶剂；将分子量为8×104Da的聚己内酯和抗肿瘤药物紫杉醇(纯度≥95％)溶于该混合溶剂中，其中紫杉醇的量占紫杉醇与聚己内酯的总质量的4％，且溶解后聚己内酯的终浓度为10％，25℃下搅拌12h，静置脱泡2h，得到静电纺丝溶液；
2)在25～35℃，相对湿度40～70％条件下将步骤1)的静电纺丝溶液放入注射器中，进行电纺，纺丝电压为8kV，纺丝流速为600μL/h；接收器为上下平行间隔布置的平行板接收器，且两板间距为10cm；注射器针头即喷丝口与接收器的水平距离为12cm；接收60min后在接收器上即可得到有序PCL/紫杉醇纳米纤维，置于真空干燥箱内以室温干燥12～24h待其溶剂完全蒸发后形成有序PCL/紫杉醇纳米纤维膜，紫杉醇负载量为4％。
扫描电镜(SEM)观察纤维平行排列度高，纤维平均直径为780nm。
实施例5
1)按质量份数计，将8份二氯甲烷和2份二甲基甲酰胺混合配制得到混合溶剂；将分子量为8×104Da的聚己内酯和抗肿瘤药物紫杉醇(纯度≥95％)溶于该混合溶剂中，其中紫杉醇的量占紫杉醇与聚己内酯的总质量的5％，且溶解后聚己内酯的终浓度为10％，25℃下搅拌12h，静置脱泡2h，得到静电纺丝溶液；
2)在25～35℃，相对湿度40～70％条件下将步骤1)的静电纺丝溶液放入注射器中，进行电纺，纺丝电压为8kV，纺丝流速为600μL/h；接收器为上下平行间隔布置的平行板接收器，且两板间距为10cm；注射器针头即喷丝口与接收器的水平距离为12cm；接收60min后在接收器上即可得到有序PCL/紫杉醇纳米纤维，置于真空干燥箱内以室温干燥12～24h待其溶剂完全蒸发后形成有序PCL/紫杉醇纳米纤维膜，紫杉醇负载量为5％。
扫描电镜(SEM)观察纤维平行排列度高，纤维平均直径为820nm。
对比例：不含抗肿瘤药物的空白对照组
1)按质量份数计，将8份二氯甲烷和2份二甲基甲酰胺混合配制得到混合溶剂；将聚己内酯溶于该混合溶剂中，25℃下搅拌12h，静置脱泡2h，得到静电纺丝溶液；该聚己内酯分子量为8×104Da；
2)在25～35℃，相对湿度40～70％条件下将步骤1)的静电纺丝溶液放入注射器中，进行电纺，纺丝电压为8kV，纺丝流速为600μL/h；接收器为上下平行间隔布置的平行板接收器，且两板间距为10cm；注射器针头即喷丝口与接收器的水平距离为12cm；接收60min后在接收器上即可得到有序PCL/紫杉醇纳米纤维，置于真空干燥箱内以室温干燥12～24h待其溶剂完全蒸发后形成有序PCL纳米纤维膜。
扫描电镜(SEM)观察纤维平行排列度高，纤维平均直径为420nm。
实验例1
利用日本JEOLJSM6701F电子显微镜对各实施例和对比例的纤维形态进行分析。其结果如图2所示，其中图2a为实施例1所收集的载药量为1％的有序纳米纤维，放大倍数为1000倍，排列性好。图2b为传统收集法得到的载药量为1％的无序纳米纤维，放大倍数为11000倍，可见，由传统无序收集法得到的纳米纤维形态不均匀，差异较大。
实验例2
利用美国Instron3345电子拉力机对实施例3、实施例4和对比例的不同药物负载量纤维膜的抗拉伸能力和抗形变能力进行分析。其结果如图3所示，随着纤维载药浓度的增加，纤维膜抗拉强度降低。
实验例3
将实施例3和实施例4的不同药物负载量纤维膜放置于PBS溶液中并绘制其释放曲线。其结果如图4所示，释放进行800h时释放总量达80％，并逐渐平稳。在药物释放过程中释放速率平稳，无突释现象，缓释效果理想。
本领域技术人员可知，当本发明的技术参数在如下范围内变化时，可以预期得到与上述实施例相同或相近的技术效果：
一种负载抗肿瘤药物的有序纳米纤维，所述纤维有序排列，纤维平均直径为530～820nm，抗肿瘤药物的负载量不大于30％，其制备方法包括：
1)按质量份数计，将6～9份第一溶剂和1～4份第二溶剂混合配制得到混合溶剂；将分子量为8×103～9×104Da的聚己内酯和抗肿瘤药物溶于该混合溶剂中，其中抗肿瘤药物的质量不超过抗肿瘤药物与聚己内酯的总质量的35％，且溶解后聚己内酯的终浓度为9～15％，25～30℃下搅拌12～24h，静置脱泡2～8h，得到静电纺丝溶液；
2)在25～35℃，相对湿度40～70％条件下将步骤1)的静电纺丝溶液进行电纺，纺丝电压为3～14kV，纺丝流速为100～1200μL/h；接收器为上下平行间隔布置的平行板接收器，且两板间距为1～100cm；喷丝口与接收器的水平距离为10～25cm；在接收器上即可得到所述之负载抗肿瘤药物的有序纳米纤维，干燥后形成有序纳米纤维膜，纤维平均直径为530～820nm，抗肿瘤药物的负载量不大于35％。
所述抗肿瘤药物的质量占抗肿瘤药物与聚己内酯的总质量的1～30％；所述抗肿瘤药物的负载量为1～30％，可以通过调整步骤1)中的抗肿瘤药物与聚己内酯的比例来得到不同负载量的有序纳米纤维，例如调整抗肿瘤药物的质量占抗肿瘤药物与聚己内酯的总质量的1％，6％，8％，10％，15％，20％，25％，30％，35％，对应得到的负载抗肿瘤药物的有序纳米纤维中的的抗肿瘤药物负载量分别为1％，6％，8％，10％，15％，20％，25％，30％，35％。
所述抗肿瘤药物为紫杉醇、多烯紫杉醇、喜树碱、依托泊苷、甲氨蝶呤中的至少一种，且药物纯度不低于95％。
所述第一溶剂为二氯甲烷、三氯甲烷、三氟乙醇、六氟异丙醇中的一种，极性较小。
所述第二溶剂为二甲基甲酰胺、二甲亚砜、甲醇、乙腈中的一种，极性较大。
所述聚己内酯用性质类似分子量相近的聚乳酸、丝素、明胶中的一种替代，其余制备方法不变，同样可得到负载抗肿瘤药物的有序纳米纤维。
根据需要，还可以在得到所述之负载抗肿瘤药物的有序纳米纤维后，在垂直于纤维排列的方向上重复电纺，吹干，即可得到纤维相互交织的有序纳米纤维膜。
以上所述，仅为本发明较佳实施例而已，故不能依此限定本发明实施的范围，即依本发明专利范围及说明书内容所作的等效变化与修饰，皆应仍属本发明涵盖的范围内。

Claims (9)

1.一种负载抗肿瘤药物的有序纳米纤维的制备方法，其特征在于：包括：
1)按质量份数计，将6～9份第一溶剂和1～4份第二溶剂混合配制得到混合溶剂；将分子量为8×103～9×104Da的聚己内酯和抗肿瘤药物溶于该混合溶剂中，其中抗肿瘤药物的质量不超过抗肿瘤药物与聚己内酯的总质量的35％，且溶解后聚己内酯的终浓度为9～15％，25～30℃下搅拌12～24h，静置脱泡2～8h，得到静电纺丝溶液；
2)在25～35℃，相对湿度40～70％条件下将步骤1)的静电纺丝溶液进行电纺，纺丝电压为3～14kV，纺丝流速为100～1200μL/h；接收器为上下平行间隔布置的平行板接收器，且两板间距为1～100cm；喷丝口与接收器的水平距离为10～25cm；在接收器上即可得到所述之负载抗肿瘤药物的有序纳米纤维，干燥后形成有序纳米纤维膜，纤维平均直径为530～820nm，抗肿瘤药物的负载量不大于35％。
2.根据权利要求1所述的一种负载抗肿瘤药物的有序纳米纤维的制备方法，其特征在于：所述抗肿瘤药物的质量占抗肿瘤药物与聚己内酯的总质量的1～30％；所述抗肿瘤药物的负载量为1～30％。
3.根据权利要求1所述的一种负载抗肿瘤药物的有序纳米纤维的制备方法，其特征在于：所述抗肿瘤药物为紫杉醇、多烯紫杉醇、喜树碱、依托泊苷、甲氨蝶呤中的至少一种，且药物纯度不低于95％。
4.根据权利要求1所述的一种负载抗肿瘤药物的有序纳米纤维的制备方法，其特征在于：所述第一溶剂为二氯甲烷、三氯甲烷、三氟乙醇、六氟异丙醇中的一种。
5.根据权利要求1所述的一种负载抗肿瘤药物的有序纳米纤维的制备方法，其特征在于：所述第二溶剂为二甲基甲酰胺、二甲亚砜、甲醇、乙腈中的一种。
6.根据权利要求1所述的一种负载抗肿瘤药物的有序纳米纤维的制备方法，其特征在于：所述聚己内酯用聚乳酸、丝素、明胶中的一种替代。
7.根据权利要求1所述的一种负载抗肿瘤药物的有序纳米纤维的制备方法，其特征在于：还包括：得到所述之负载抗肿瘤药物的有序纳米纤维后，在垂直于纤维排列的方向上重复电纺步骤，干燥，得到纤维相互交织的有序纳米纤维膜。
8.根据权利要求1至7中任一项所述的制备方法制备的负载抗肿瘤药物的有序纳米纤维在制备抗肿瘤药物中的应用。
9.一种负载抗肿瘤药物的有序纳米纤维，其特征在于：所述纤维有序排列，纤维平均直径为530～820nm，抗肿瘤药物的负载量不大于30％。
CN201510915089.9A 2015-12-10 2015-12-10 一种负载抗肿瘤药物的有序纳米纤维及其制备方法 Active CN105543998B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510915089.9A CN105543998B (zh) 2015-12-10 2015-12-10 一种负载抗肿瘤药物的有序纳米纤维及其制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510915089.9A CN105543998B (zh) 2015-12-10 2015-12-10 一种负载抗肿瘤药物的有序纳米纤维及其制备方法

Publications (2)

Publication Number Publication Date
CN105543998A true CN105543998A (zh) 2016-05-04
CN105543998B CN105543998B (zh) 2018-02-23

Family

ID=55823546

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510915089.9A Active CN105543998B (zh) 2015-12-10 2015-12-10 一种负载抗肿瘤药物的有序纳米纤维及其制备方法

Country Status (1)

Country Link
CN (1) CN105543998B (zh)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105944145A (zh) * 2016-06-16 2016-09-21 浙江理工大学 具有促进成骨细胞方向性生长和迁移的支架制备方法
CN107308136A (zh) * 2017-07-05 2017-11-03 西南大学 一种载抗肿瘤药物电纺微米纤维膜及其制备方法
CN107737119A (zh) * 2017-11-10 2018-02-27 华侨大学 一种pcl‑plga缓释制剂及其制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101843578A (zh) * 2010-05-14 2010-09-29 东华大学 一种载抗肿瘤光敏剂纳米纤维膜及其制备方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101843578A (zh) * 2010-05-14 2010-09-29 东华大学 一种载抗肿瘤光敏剂纳米纤维膜及其制备方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
OLGA HARTMAN ET AL.: "Biofunctionalization of electrospun PCL-based scaffolds with perlecan domain IV peptide to creat a 3-D pharmacokinetic cancer model", 《BIOMATERIALS》 *
仰大勇等: "静电纺丝制备有序纳米纤维的研究进展", 《合成纤维》 *
朱晓东等: "SN-38缓释系统的制作及其抗胶质瘤作用的体外实验研究", 《山东大学学报( 医学版)》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105944145A (zh) * 2016-06-16 2016-09-21 浙江理工大学 具有促进成骨细胞方向性生长和迁移的支架制备方法
CN107308136A (zh) * 2017-07-05 2017-11-03 西南大学 一种载抗肿瘤药物电纺微米纤维膜及其制备方法
CN107737119A (zh) * 2017-11-10 2018-02-27 华侨大学 一种pcl‑plga缓释制剂及其制备方法

Also Published As

Publication number Publication date
CN105543998B (zh) 2018-02-23

Similar Documents

Publication Publication Date Title
Wei et al. Mass production of nanofibers from needleless electrospinning by a novel annular spinneret
Chen et al. The influence of fiber diameter of electrospun poly (lactic acid) on drug delivery
Van der Schueren et al. An alternative solvent system for the steady state electrospinning of polycaprolactone
Casasola et al. Electrospun poly lactic acid (PLA) fibres: Effect of different solvent systems on fibre morphology and diameter
Liu et al. Controllable structure, properties, and degradation of the electrospun PLGA/PLA‐blended nanofibrous scaffolds
Erickson et al. High-throughput and high-yield fabrication of uniaxially-aligned chitosan-based nanofibers by centrifugal electrospinning
Crabbe-Mann et al. Ethyl cellulose, cellulose acetate and carboxymethyl cellulose microstructures prepared using electrohydrodynamics and green solvents
Chen et al. Dexamethasone loaded core–shell SF/PEO nanofibers via green electrospinning reduced endothelial cells inflammatory damage
Yang et al. Preparation of porous core–shell poly L-lactic acid/polyethylene glycol superfine fibres containing drug
Bak et al. Effect of humidity and benign solvent composition on electrospinning of collagen nanofibrous sheets
CN105239206B (zh) 一种聚己内酯/聚乙二醇复合串珠状纤维及其制备方法
CN105543998A (zh) 一种负载抗肿瘤药物的有序纳米纤维及其制备方法
CN102586920A (zh) 一种聚丙烯腈纳米纤维的制备方法
Kalluri et al. Effect of electrospinning parameters on the fiber diameter and morphology of PLGA nanofibers
Xin et al. Core–sheath functional polymer nanofibers prepared by co-electrospinning
CN103243407A (zh) 一种以无针静电纺丝技术制备皮芯结构载药纳米纤维的方法
Liu et al. Controlled dual drug release and in vitro cytotoxicity of electrospun poly (lactic-co-glycolic acid) nanofibers encapsulated with micelles
Kruse et al. Electro-spun PLA-PEG-yarns for tissue engineering applications
CN103276470B (zh) 一种PLGA/MNPs纳米复合纤维材料及其制备与应用
CN104287869B (zh) 一种用于气管移植的新型纳米纤维膜/纱支架及其制备方法
Xu et al. Electrospun nanoporous materials: reality, potential and challenges
Lin et al. Property evaluation of Bletilla striata/polyvinyl alcohol nano fibers and composite dressings
Zheng et al. Effects of cylindrical-electrode-assisted solution blowing spinning process parameters on polymer nanofiber morphology and microstructure
Xie et al. Fabrication of bioactive glass particles composite porous fibers by combination of electrospinning and phase separation
CN104911738A (zh) 一种pu/cap芯鞘结构纤维的制备方法

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant