染料木黄酮泊洛沙姆P407/P403混合胶束的制备及药动学研究

doi:10.5246/jcps.2018.05.035

中国药学(英文版) ›› 2018, Vol. 27 ›› Issue (5): 342-351.DOI: 10.5246/jcps.2018.05.035

染料木黄酮泊洛沙姆P407/P403混合胶束的制备及药动学研究

蔡雁¹, 戴巍³, 钦富华^2*, 孙洁胤², 魏瑞龙²

1. 宁波市第九医院药剂科, 浙江宁波 315020
2. 浙江医药高等专科学校, 浙江宁波 315100
3. 杭州东祥医药科技有限公司, 浙江杭州 310051

收稿日期:2018-01-13 修回日期:2018-03-20 出版日期:2018-05-31 发布日期:2018-05-11
通讯作者: Tel.: +86-574-88225752, E-mail: qinfh@mail.zjpc.net.cn
基金资助:
The Zhejiang Public Welfare Technology Application Research Project (Grant No. 2015C31100) and the Ningbo Science and Technology Innovation Team Project (Grant No. 2015C110027).

Genistein-loaded poloxamer 403/407 mixed micelles: preparation and pharmacokinetic study in rats

Yan Cai¹, Wei Dai³, Fuhua Qin^2*, Jieyin Sun², Ruilong Wei²

1. Department of Pharmacy, Ningbo NO. 9 Hospital, Ningbo 315020, China
2. Department of Pharmeucital Engineering, Zhejiang Pharmaceutical College, Ningbo 315100, China
3. Hangzhou Dongxiang Pharmaceutical Technology Co., Ltd., Hangzhou 310051, China

Received:2018-01-13 Revised:2018-03-20 Online:2018-05-31 Published:2018-05-11
Contact: Tel.: +86-574-88225752, E-mail: qinfh@mail.zjpc.net.cn
Supported by:
The Zhejiang Public Welfare Technology Application Research Project (Grant No. 2015C31100) and the Ningbo Science and Technology Innovation Team Project (Grant No. 2015C110027).

摘要/Abstract

摘要：

本文主要制备载染料木黄酮的泊洛沙姆403/407混合聚合物胶束,以改善染料木黄酮的溶解度和口服生物利用度。研究采用薄膜分散法制备混合胶束,考察其形态,粒径, zeta电位,包封率和载药量;采用膜透析法考察其体外释药行为;以混悬液为对照,对混合胶束在大鼠体内的药物动力学过程进行了研究。结果显示所制备的混合胶束形态圆整,粒径均一,平均粒径为(20.31±0.43) nm, PDI为0.193, zeta电位为(–8.94±0.35) mV;包封率为和载药量分别为(90.59±0.67)%和(7.74±0.05)%; 染料木黄酮在混合胶束中的溶解度达到3.80 mg/mL,比水中的溶解度提高了约130倍。混合胶束在体外呈现缓释特征,且无突释现象,但释放速度快于混悬液;大鼠灌胃混合胶束和混悬液的药动学结果显示混合胶束的AUC₀_–_t和AUC₀_–_∞分别为GEN混悬液的196.74%和204.62%,表明所制备的混合胶束显著地提高了染料木黄酮的溶解度和口服生物利用度。

关键词: 染料木黄酮, 泊洛沙姆, 混合胶束, 药动学

Abstract:

In the present study, we aimed to prepare poloxamer 403/407 mixed micelles in order to improve the solubility and oral bioavailability of genistein.Genistein was incorporated in the mixed poloxamer micelles by thin-film hydration method, and its physicochemical properties, including particle size, zeta potential, entrapment efficiency and drug loading, were investigated.In vitro release of genistein from the mixed micelles was monitored by dialysis method, and pharmacokinetic study of genistein loaded mixed micelles was carried out in rats. We found that the particle size and zeta potential of mixed micelles were (20.31±0.43) nm and (–8.94±0.35) mV, with encapsulation efficiency 90.59%±0.67% and drug loading 7.74%±0.05%. Solubility of genistein in mixed micelles reached 3.80 mg/mL, which was about 130 times higher than that in water.Genistein-loaded mixed micelles showed sustained release characteristics in vitro with no burst release phenomenon, but it was faster than suspension.The AUC₀_–_tandAUC₀_–_∞of mixed micelles were 196.74% and 204.62% greater than that of genisein suspension, respectively.Consequently,poloxamer 403/407 mixed micelles significantly improved the solubility and oral bioavailability of genistein, which could be used as an effective drug delivery system for oral administration of poorly soluble drugs.

Key words: Genistein, Poloxamer 407, Poloxamer 403, Micelles, Pharmacokinetics

中图分类号:

R969.1

Supporting:

蔡雁, 戴巍, 钦富华, 孙洁胤, 魏瑞龙. 染料木黄酮泊洛沙姆P407/P403混合胶束的制备及药动学研究[J]. 中国药学(英文版), 2018, 27(5): 342-351.

Yan Cai, Wei Dai, Fuhua Qin, Jieyin Sun, Ruilong Wei. Genistein-loaded poloxamer 403/407 mixed micelles: preparation and pharmacokinetic study in rats[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(5): 342-351.

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染料木黄酮泊洛沙姆P407/P403混合胶束的制备及药动学研究

Genistein-loaded poloxamer 403/407 mixed micelles: preparation and pharmacokinetic study in rats

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