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(铜 - 姜黄素)β - 环糊精阴道凝胶:为局部避孕预防开发提供一种新型金属 - 草药方法。

(Copper-curcumin) β-cyclodextrin vaginal gel: delivering a novel metal-herbal approach for the development of topical contraception prophylaxis.

作者信息

Gaurav Chauhan, Goutam Rath, Rohan Kesarkar N, Sweta Kothari T, Abhay Chowdhary S, Amit Goyal K

机构信息

DBT Lab, Indo-Soviet Friendship College of Pharmacy, Moga, Punjab, India.

Department of Virology, Haffkine Institute for Training Research and Testing, Parel, Mumbai, India.

出版信息

Eur J Pharm Sci. 2014 Dec 18;65:183-91. doi: 10.1016/j.ejps.2014.09.019. Epub 2014 Sep 28.


DOI:10.1016/j.ejps.2014.09.019
PMID:25266573
Abstract

Delivering a safe and effective topical vaginal contraceptive is the need of present era. We explored the potential of a metal (copper) and herbal moiety (curcumin) for this topical contraceptive prophylaxis. Complex of copper and curcumin (Cu-Cur) was synthesized and the concerns regarding its aqueous solubility was resolved by including it into the hydrophobic cavity of β-cyclodextrin (β-CD) as (Cu-Cur)CD inclusion complex. Dose assessment was made on the basis of in-vitro spermicidal assays and cell cytotoxicity studies. Finally the (Cu-Cur)CD loaded vaginal gel was prepared, characterized and evaluated for in-vitro spermicidal activity and preclinical toxicity studies. Spectral and morphological characterizations confirmed the synthesis of (Cu-Cur) and (Cu-Cur)CD inclusion complex. Spermicidal assays and Hela cell cytotoxic data revealed an optimized 1.5% (Cu-Cur)CD for further studies. 1.5% w/w (Cu-Cur)CD loaded carbopol 974p gel provided 100% motility even at 2-fold dilution and preclinical toxicity studies in Rats and Rabbits revealed its highly safe profile. The hypothesis of considering metal-herbal complex and its cyclodextrin complex has worked and the well planned strategy of including it in (β-CD) cavity provided a preeminent platform for vaginal delivery. In-vitro assays and preclinical toxicity analysis confirmed its potential to be used as highly safe and effective prophylaxis.

摘要

提供一种安全有效的阴道局部用避孕药是当今时代的需求。我们探索了金属(铜)和草药成分(姜黄素)用于这种局部避孕预防的潜力。合成了铜和姜黄素的复合物(Cu-Cur),并通过将其包合到β-环糊精(β-CD)的疏水腔内形成(Cu-Cur)CD包合物来解决其水溶性问题。基于体外杀精试验和细胞毒性研究进行剂量评估。最后制备了负载(Cu-Cur)CD的阴道凝胶,对其进行表征,并评估其体外杀精活性和临床前毒性研究。光谱和形态表征证实了(Cu-Cur)和(Cu-Cur)CD包合物的合成。杀精试验和Hela细胞毒性数据显示,优化后的(Cu-Cur)CD浓度为1.5%,可用于进一步研究。含1.5%w/w(Cu-Cur)CD的卡波姆974p凝胶即使在2倍稀释时仍能提供100%的精子活力,在大鼠和兔子身上进行的临床前毒性研究表明其具有高度安全性。考虑金属-草药复合物及其环糊精复合物的假设是可行的,将其包合到(β-CD)腔内的精心设计策略为阴道给药提供了一个卓越的平台。体外试验和临床前毒性分析证实了其作为高度安全有效的预防药物的潜力。

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