mPEG-PLA共聚物胶束对DHA的增溶及光保护作用
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摘要
以聚乙二醇单甲醚(mPEG)和外消旋丙交酯(D,L-LA)为原料,采用开环聚合法合成聚乙二醇单甲醚-聚乳酸(mPEG-PLA)共聚物,并用溶剂挥发法制备包载双氢青蒿素(DHA)的共聚物胶束(DHA/mPEG-PLA)。利用红外光谱(FT-IR)、核磁共振氢谱(1 H-NMR)和接触角测量仪研究了共聚物的结构和性质;利用激光粒度分析仪和扫描电镜(SEM)研究了胶束的粒径和形貌。结果表明mPEG-PLA共聚物的临界胶束浓度(CMC)为7.71mg/L。DHA/mPEG-PLA共聚物胶束呈球形,平均粒径(118.1±1.9)nm,载药量和包封率分别为(2.7±0.1)%和(77.1±0.3)%。胶束对DHA的水相表观溶解度增大约1.5倍。紫外光光照39h,纯DHA在混悬液中降解率达37%且持续增长,胶束中DHA降解率达到10%后基本保持不变。
The methoxy poly(ethylene glycol)-poly(lactic acid)(mPEG-PLA)copolymer was synthesized by ring opening polymerization using methoxy poly(ethylene glycol)(mPEG)and D,L-lactide(D,L-LA).The dihydroartemisinin(DHA)-loaded copolymer micelles(DHA/mPEG-PLA)were prepared via solvent evaporation method.The chemical structure and property of copolymer were characterized by Infrared Spectroscopy(IR),proton Nuclear Magnetic Resonance(1 H-NMR)and contact angle measuring instrument.The size and morphology of the micelles were investigated by Nano ZS90 Zetasizer and Scanning Electron Microscopy(SEM).Results showed that the critical micelle concentration(CMC)of copolymer was 7.71 mg/L.The DHA/mPEG-PLA copolymer micelles were spherical in shape with average particle sizes of(118.1±1.9)nm,the entrapment efficiency and the loading capacity were(77.1±0.3)%and(2.7±0.1)%,respectively.The apprarent solubility of DHA in micellar solution was increased about 1.5 times as compared with DHA in aqueous solution.After 39 hof UV irradiation,the degradation rate of DHA in suspension was 37% and it still showed a rising trend,while the degradation rate in micelles tended to be a constant(10%).
The methoxy poly(ethylene glycol)-poly(lactic acid)(mPEG-PLA)copolymer was synthesized by ring opening polymerization using methoxy poly(ethylene glycol)(mPEG)and D,L-lactide(D,L-LA).The dihydroartemisinin(DHA)-loaded copolymer micelles(DHA/mPEG-PLA)were prepared via solvent evaporation method.The chemical structure and property of copolymer were characterized by Infrared Spectroscopy(IR),proton Nuclear Magnetic Resonance(1 H-NMR)and contact angle measuring instrument.The size and morphology of the micelles were investigated by Nano ZS90 Zetasizer and Scanning Electron Microscopy(SEM).Results showed that the critical micelle concentration(CMC)of copolymer was 7.71 mg/L.The DHA/mPEG-PLA copolymer micelles were spherical in shape with average particle sizes of(118.1±1.9)nm,the entrapment efficiency and the loading capacity were(77.1±0.3)%and(2.7±0.1)%,respectively.The apprarent solubility of DHA in micellar solution was increased about 1.5 times as compared with DHA in aqueous solution.After 39 hof UV irradiation,the degradation rate of DHA in suspension was 37% and it still showed a rising trend,while the degradation rate in micelles tended to be a constant(10%).
引文
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[15]ZHANG Hanwei,BEI Jianzhong,WANG Shenguo.Preparation and drug release behaviors of 5-fluorouracil loaded poly(glycolide-co-lactide-co-caprolactone)nanoparticles[J].Journal of Applied Polymer Science,2007,106(6):3757-3767.
[2]LI Hongjun,WANG Wei,QU Guoli,et al.Effect of the in vivo activity of dihydroartemisinin against Schistosoma mansoni infection in mice[J].Parasitology Research,2012,110(5):1727-1732.
[3]ZHOU Zhonghai,CHEN Fuxing,XU Wenrong,et al.Enhancement effect of dihydroartemisinin on humanγδT cell proliferation and killing pancreatic cancer cells[J].International Immunopharmacology,2013,17(3):850-857.
[4]GABRILS M,PLAIZIER-VERCAMMEN J.Design of a dissolution system for the evaluation of the release rate characteristics of artemether and dihydroartemisinin from tablets.[J].International Journal of Pharmaceutics,2004,274(1/2):245-260.
[5]RIGHESCHI C,CORONNELLO M,MASTRANTONI A,et al.Strategy to provide a useful solution to effective delivery of dihydroartemisinin:Development,characterization and in vitro,studies of liposomal formulations[J].Colloids&Surfaces B Biointerfaces,2014,116(2):121-127.
[6]陈方伟,郭涛,李海燕,等.双氢青蒿素羟丙基-β-环糊精包合物的制备与表征[J].药学学报,2012(4):529-534.
[7]LEE K S,CHUNG H C,IM S A,et al.Multicenter phaseⅡtrial of Genexol-PM,a novel Cremophor-free,polymeric micelle formulation of paclitaxel,with cisplatin in patients with advanced non-small-cell lung cancer[J].Annals of Oncology,2007,18(12):2009-2014.
[8]ANGELOPOULOU A,VOULGARI E,DIAMANTI E K,et al.Graphene oxide stabilized by PLA-PEG copolymers for the controlled delivery of paclitaxel.[J].European Journal of Pharmaceutics&Biopharmaceutics,2015,93:18-26.
[9]NICOLAS J,MURA S,BRAMBILLA D,et al.Design,functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery.[J].Chem Inform,2013,42(23):1147-1235.
[10]COUMES F,HUANG C Y,HUANG C H,et al.Design and development of immunomodulatory antigen delivery systems based on peptide/PEG-PLA conjugate for tuning immunity[J].Biomacromolecules,2015,16(11):3666-3673.
[11]JUNG K H,LEE J H,PARK J W,et al.Resveratrol-loaded polymeric nanoparticles suppress glucose metabolism and tumor growth in vitro and in vivo[J].International Journal of Pharmaceutics,2015,478(1):251-257.
[12]JUN Y J,MIN J H,JI D E,et al.A micellar prodrug of paclitaxel conjugated to cyclotriphosphazene.[J].Bioorganic&Medicinal Chemistry Letters,2008,18(24):6410-6413.
[13]SEON Jungjung,MIN Hee Park,HYO Jung Moon,et al.Thermal gelation or gel melting:(Ethylene glycol)113-(Lalanine)12,and(ethylene glycol)113-(L-lactic acid)12[J].Journal of Polymer Science Part A Polymer Chemistry,2014,52(17):2434-2441.
[14]林晖,胡勇有,张潇予,等.不同组分鼠李糖脂的胶束性质及其对三氯生的增溶作用[J].环境科学学报,2011,31(12):2609-2615.
[15]ZHANG Hanwei,BEI Jianzhong,WANG Shenguo.Preparation and drug release behaviors of 5-fluorouracil loaded poly(glycolide-co-lactide-co-caprolactone)nanoparticles[J].Journal of Applied Polymer Science,2007,106(6):3757-3767.