壳寡糖修饰的盐酸川芎嗪mPEG-PLGA微球的制备及体外释放特性
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摘要
目的以单甲氧基聚乙二醇-聚乳酸羟基乙酸共聚物(mPEG-PLGA)为载体制备盐酸川芎嗪(TMPH)微球,用壳寡糖(COS)对微球进行修饰,并对其包封前后的体外药物释放行为进行考察。方法采用复乳-溶剂挥发法制备壳寡糖修饰的盐酸川芎嗪缓释微球,通过单因素试验,以包封率为评价指标,考察影响微球质量的因素,采用正交试验进行优化,筛选出最佳的处方,并进行体外释药性能的考察。结果 mPEG-PLGA浓度为50 g/L,药物浓度为30 g/L,内水相/油相比为1:10,外水相油相比为4:1,最佳处方制备的盐酸川芎嗪微球表面光滑圆整,包封率在60%以上。经壳寡糖修饰后微球突释效应减少。结论以mPEG-PLGA为载体材料,采用复乳-溶剂挥发法可以制备包封率较高的盐酸川芎嗪微球,壳寡糖修饰有减小突释效应的作用。
Objective To prepare tetramethylpyrazine hydrochloride microspheres with methoxy poly(ethylene glycol)-poly(lactide-co-glycolide)copolymer(mPEG-PLGA). Microspheres were modified with chitosan oligosaccharide(COS). The in vitro drug release behavior were investigated before and after the modification.Methods Tetramethylpyrazine hydrochloride microspheres modified with COS were prepared by emulsion-solvent evaporation method. The influence of formulation and manufacture was studied by the single factor experiments. The optimal formulation was verified by Orthogonal experimental. The characteristics of drug release were determined in vitro.Results The optimum prescription was 50 g/L mPEG-PLGA,30 g/L Ligustrazine,internal water phase:oil phase=1:10,external water phase:oil phase=4:1. The surface of Ligustrazine microspheres prepared with optimal prescription was with a good appearance without adhesions. The encapsulation efficiency was over 60%. The burst effect of microspheres modified with COS was decreased.Conclusion Emulsion-solvent evaporation method was developed to prepare mPEG-PLGA tetramethylpyrazine microspheres with higher entrapment efficiency. The microspheres modified with COS could decrease burst effect.
Objective To prepare tetramethylpyrazine hydrochloride microspheres with methoxy poly(ethylene glycol)-poly(lactide-co-glycolide)copolymer(mPEG-PLGA). Microspheres were modified with chitosan oligosaccharide(COS). The in vitro drug release behavior were investigated before and after the modification.Methods Tetramethylpyrazine hydrochloride microspheres modified with COS were prepared by emulsion-solvent evaporation method. The influence of formulation and manufacture was studied by the single factor experiments. The optimal formulation was verified by Orthogonal experimental. The characteristics of drug release were determined in vitro.Results The optimum prescription was 50 g/L mPEG-PLGA,30 g/L Ligustrazine,internal water phase:oil phase=1:10,external water phase:oil phase=4:1. The surface of Ligustrazine microspheres prepared with optimal prescription was with a good appearance without adhesions. The encapsulation efficiency was over 60%. The burst effect of microspheres modified with COS was decreased.Conclusion Emulsion-solvent evaporation method was developed to prepare mPEG-PLGA tetramethylpyrazine microspheres with higher entrapment efficiency. The microspheres modified with COS could decrease burst effect.
引文
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[11]宋克东,刘天庆,郭文华,等.包埋PLGA微球的可控释壳聚糖支架材料的研究[J].高校化学工程学报,2010,24(6):988.
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[14]李丹丹,马英,柏韵,等.响应面法优化微波辅助果胶酶制备壳寡糖的工艺[J].食品工业科学,2018,5(12):36.
[15] Ma Y,Huang Q,Lv MY,et al.Chitosan-Zn chelate increases antioxidant enzyme activity and improves immune function in weaned piglets[J].Biol Trace Elem Res,2014,158(1):45-50.
[2]彭春梅,张宇,唐勤,等.川芎嗪缓控释制剂的研究进展[J].中成药,2013,4(35):811-812.
[3]王生,赵杨,陶丽,等.川芎嗪对肿瘤介导的血液高凝的影响[J].中国药理学通报,2012,28(5):709-715.
[4]李健,于耀宇,赵振伟,等.罂粟碱明胶微球的合成和体外药物释放研究[J].医学研究生学报,2010,23(1):13-14.
[5] Airen X,Mingfei Y,Guangkui X,et al.A physical model for thesize-dependent cellular uptake of nanoparticles modified with cationicsurfactants[J].Int J Nanomed,2012,7(28):3547-3554.
[6]王丽.磷酸川芎嗪制剂研究进展[J].科学技术创新,2018,11(27):46-47.
[7]何晋浙,姚丽娜,孙培龙.响应面试验优化猴头菌素-PLGA微球制备工艺及其体外释药性能[J].食品科学,2017,38(6):242-244.
[8]孙丹丹,王志国,焦玥,等.盐酸川芎嗪在冷冻干燥工艺中的稳定性研究[J].药物评价研究,2018,41(1):100-102.
[9] Meng FT,Ma GH,Qiu W,et al.W/O/W double emulsion technique using ethyl acetate as organic solvent:effects of its diffusion rate on the characteristics of microparticles[J].Control Release,2003,91(3):407.
[10]戎堃,刘彬丽,李木子,等.不锈钢膜乳化法制备PLGA微球的初步研究与评价[J].中国中药杂志,2014,39(4):1230-1321.
[11]宋克东,刘天庆,郭文华,等.包埋PLGA微球的可控释壳聚糖支架材料的研究[J].高校化学工程学报,2010,24(6):988.
[12]李家萌,杨毅梅.基于纳米技术的中药现代化研究现状[J].医学研究生学报,2016,6(29):648-650.
[13]吕丕平,王玉霞,崔一民,等.蛋白类药物缓释微球制剂的研究进展[J].临床药物治疗杂志,2015,13(3):5-9.
[14]李丹丹,马英,柏韵,等.响应面法优化微波辅助果胶酶制备壳寡糖的工艺[J].食品工业科学,2018,5(12):36.
[15] Ma Y,Huang Q,Lv MY,et al.Chitosan-Zn chelate increases antioxidant enzyme activity and improves immune function in weaned piglets[J].Biol Trace Elem Res,2014,158(1):45-50.