姜黄素/聚(α-氰基丙烯酸异丁酯)载药微球的制备及其药物释放
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摘要
以α-氰基丙烯酸异丁酯(iBCA)为原料、泊洛沙姆188为乳化剂,以捏合法制得的姜黄素(Cur)/羟丙基-β-环糊精(HP-β-CD)包合物(Cur-HP-β-CD)为负载药物,经一步乳化法制得姜黄素/聚(α-氰基丙烯酸异丁酯)载药微球(Cur-HP-β-CD-PiBCA)。考察乳化剂、负载药物的浓度对微球粒径与分布、微球载药率及包封率的影响,并对载药微球的药物释放进行了研究。结果表明:随着乳化剂浓度从0.01%增加到0.07%,载药微球粒径下降,粒径分布变宽,载药率和包封率均增加,适宜的乳化剂浓度为0.05%;随着药物浓度从0.03%增加到0.07%,微球载药率升高,包封率下降;载药微球的载药率越高,最终的药物累积释放百分率越低。姜黄素经包合和负载,不仅可以有效改善其亲水性,而且可以提高其溶出度,为提高姜黄素的生物利用度奠定了基础。
Curcumin-loaded poly(α-isobutyl cyanoacrylate) microspheres(Cur-HP-β-CD-PiBCA) were prepared by one-step emulsification with α-isobutyl cyanoacrylate as materials,poloxamer 188 as emulsifier,and curcumin complex with hydroxypropyl-β-cyclodextrin(Cur-HP-β-CD) as drug prepared by kneading method.Effects of emulsifier and drug concentration on microspheres size and distribution,drug loading and encapsulation efficiency were investigated in detail.And the curcumin release of drug-loaded microspheres was also studied.Results showed that as the emulsifier concentration increased from 0.01% to 0.07%,particle size of the drug-loaded microspheres decreased while particle size distribution,drug loading and entrapment efficiency increased.The optimized concentration of surfactant was 0.05%.With increasing the concentration of drug from 0.03% to 0.07%,drug loading of Cur-HP-β-CD-PiBCA increased,but encapsulation efficiency decreased.Additionally,the results of drug release experiments revealed that the higher drug loading of Cur-HP-β-CD-PiBCA was,the lower cumulative release percentage was.Drug-loading of cumulative inclusions in HP-β-CD by PiBCA can improve its wettability,and increase the degree of dissolution and bioavailability.
Curcumin-loaded poly(α-isobutyl cyanoacrylate) microspheres(Cur-HP-β-CD-PiBCA) were prepared by one-step emulsification with α-isobutyl cyanoacrylate as materials,poloxamer 188 as emulsifier,and curcumin complex with hydroxypropyl-β-cyclodextrin(Cur-HP-β-CD) as drug prepared by kneading method.Effects of emulsifier and drug concentration on microspheres size and distribution,drug loading and encapsulation efficiency were investigated in detail.And the curcumin release of drug-loaded microspheres was also studied.Results showed that as the emulsifier concentration increased from 0.01% to 0.07%,particle size of the drug-loaded microspheres decreased while particle size distribution,drug loading and entrapment efficiency increased.The optimized concentration of surfactant was 0.05%.With increasing the concentration of drug from 0.03% to 0.07%,drug loading of Cur-HP-β-CD-PiBCA increased,but encapsulation efficiency decreased.Additionally,the results of drug release experiments revealed that the higher drug loading of Cur-HP-β-CD-PiBCA was,the lower cumulative release percentage was.Drug-loading of cumulative inclusions in HP-β-CD by PiBCA can improve its wettability,and increase the degree of dissolution and bioavailability.
引文
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9 Doppalapudi S, Jain A, Khan W, et al. Biodegradable polymers-an overview. Polym Adv Technol, 2014,25(5, SI):427-435.
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12张强,廖工铁,硫酸庆大霉素聚氰基丙烯酸正丁酯毫微球制备工艺研究.中国药学杂志,1996, 31(1):24-27.
13 Maskarinec S A, Hannig J, Lee R C, et al. Direct observation of poloxamer 188 insertion into lipid monolayers. Biophys J, 2002,82(3):1453-1459.
14 Mitra A, Lin Senshang. Effect of surfactant on fabrication and characterization of paclitaxel-loaded polybutylcyanoacrylate nanoparticulate delivery systems. J Pharm Pharmacol, 2003, 55(7):895-902.
15 Illum L, Khan M, Mak E. Evaluation of carrier capacity and release characteristics for poly(butyl 2-cyanoacrylate)nanoparticles. Int J Pharm, 1986, 30(1):17-28.
2韩刚,霍文,李秋影.姜黄素的稳定性研究.中成药,2007, 29(2):291-293.
3杨鹏波,张华.脂质体的研究新进展.浙江中医药大学学报,2013,37(7):936-939.
4张盛伟,李湘洲,李文生,等.姜黄素纳米混悬剂的制备及其表征.林产化学与工业,2016, 36(2):109-114.
5 Liu Jieying, Chen Siyuan, Lv Li, et al. Recent progress in studying curcumin and its nano-preparations for cancer therapy. Curr Pharm Des,2013,19(11):1974-1993.
6 Duan Jinghua, Zhang Yangde, Han Shiwei, et al. Synthesis and in vitro/in vivo anti-cancer evaluation of curcumin-loaded chitosan/poly(butyl cyanoacrylate)nanoparticles. Int J Pharm,2010,400(1/2):211-220.
7 Mulik R, Mahadik K, Paradkar A. Development of curcuminoids loaded poly(butyl)cyanoacrylate nanoparticles:Physicochemical characterization and stability study. Eur J Pharm Sci, 2009,37(3/4):395-404.
8 Hani U, Shivakumar H G, Srivastava A, et al. Design and optimization of curcumin-HPβCD bioadhesive vaginal tablets by 23factorial design:in vitro and in vivo evaluation. J Pharm Innov,2015,10(1):21-35.
9 Doppalapudi S, Jain A, Khan W, et al. Biodegradable polymers-an overview. Polym Adv Technol, 2014,25(5, SI):427-435.
10 Curic A, Keller B L, Reul R A, et al. Development and lyophilization of itraconazole loaded poly(butyl cyanoacrylate)nanospheres as a drug delivery system. Eur J Pharm Sci, 2015,78(14):121-131.
11 Tian Xinhua, Lin Xiaoning, Wei Feng, et al. Enhanced brain targeting of temozolomide in polysorbate-80 coated polybutylcyanoacrylate nanoparticles. Int J Nanomedicine, 2011,6(6):445-452.
12张强,廖工铁,硫酸庆大霉素聚氰基丙烯酸正丁酯毫微球制备工艺研究.中国药学杂志,1996, 31(1):24-27.
13 Maskarinec S A, Hannig J, Lee R C, et al. Direct observation of poloxamer 188 insertion into lipid monolayers. Biophys J, 2002,82(3):1453-1459.
14 Mitra A, Lin Senshang. Effect of surfactant on fabrication and characterization of paclitaxel-loaded polybutylcyanoacrylate nanoparticulate delivery systems. J Pharm Pharmacol, 2003, 55(7):895-902.
15 Illum L, Khan M, Mak E. Evaluation of carrier capacity and release characteristics for poly(butyl 2-cyanoacrylate)nanoparticles. Int J Pharm, 1986, 30(1):17-28.