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通过分散于黏膜黏附凝胶中的脂质体经阴道给药盐酸苄达明。

Vaginal Delivery of Benzydamine Hydrochloride through Liposomes Dispersed in Mucoadhesive Gels.

作者信息

Tuğcu-Demiröz Fatmanur

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmacy, Gazi University.

出版信息

Chem Pharm Bull (Tokyo). 2017 Jul 1;65(7):660-667. doi: 10.1248/cpb.c17-00133. Epub 2017 Apr 22.

Abstract

Liposomal vaginal drug delivery systems are important strategy in the treatment of both topical and systemic diseases. The aim of this study was to develop a vaginal delivery system for benzydamine hydrochloride (BNZ) loaded liposomes dispersed into mucoadhesive gels. The delivery system was also designed for a once a day dosage and to obtain controlled release of the BNZ. For this purpose BNZ containing gel formulations using hydroxypropyl methylcellulose (HPMC) K100M and Carbopol 974P, which are composed of polymers that show promising potential as mucoadhesive vaginal delivery systems, were developed. In addition, a BNZ containing liposome formulation was developed for vaginal administration. To improve the vaginal retention time, liposome was incorporated in HPMC K100M and Carbopol 974P gel formulations. This system is called lipogel. The developed BNZ liposomes have a slightly negative zeta potential (-1.50±0.16 mV), a 2.25±0.009 µm particle size and a 34% entrapment efficiency. These gels and lipogels have appropriate pH, viscosity, textural properties and mucoadhesive value for vaginal administration. Lipogels were found to be the best formulations for in vitro diffusion and ex vivo mucoadhesion. The work of mucoadhesion obtained from liposomes was in the range of 0.027±0.045 and 0.030±0.017 mJ/cm, while the value obtained from lipogels was between 0.176±0.037 and 0.243±0.53 mJ/cm. N1 and N2 lipogel formulations diffused 57 and 67% of BNZ respectively at the end of 24 h. Moreover, a higher mucoadhesion, which increases drug residence time in comparison to liposomes, could improve BNZ efficacy. In conclusion, BNZ mucoadhesive vaginal lipogel formulations can be promising alternatives to traditional dosage forms for vaginal topical therapy.

摘要

脂质体阴道给药系统是治疗局部和全身性疾病的重要策略。本研究的目的是开发一种将载有盐酸苄达明(BNZ)的脂质体分散到粘膜粘附凝胶中的阴道给药系统。该给药系统还设计为每日一次给药剂量,并实现BNZ的控释。为此,开发了使用羟丙基甲基纤维素(HPMC)K100M和卡波姆974P的含BNZ凝胶制剂,它们由作为粘膜粘附阴道给药系统具有广阔潜力的聚合物组成。此外,还开发了一种用于阴道给药的含BNZ脂质体制剂。为了提高阴道滞留时间,将脂质体掺入HPMC K100M和卡波姆974P凝胶制剂中。该系统称为脂质凝胶。所制备的BNZ脂质体具有略微负的zeta电位(-1.50±0.16 mV)、2.25±0.009 µm的粒径和34%的包封率。这些凝胶和脂质凝胶具有适合阴道给药的pH值、粘度、质地特性和粘膜粘附值。发现脂质凝胶是体外扩散和离体粘膜粘附的最佳制剂。脂质体的粘膜粘附功在0.027±0.045和0.030±0.017 mJ/cm范围内,而脂质凝胶的值在0.176±0.037和0.243±0.53 mJ/cm之间。N1和N2脂质凝胶制剂在24小时结束时分别扩散了57%和67%的BNZ。此外,与脂质体相比,更高的粘膜粘附性增加了药物停留时间,可以提高BNZ的疗效。总之,BNZ粘膜粘附性阴道脂质凝胶制剂可能是阴道局部治疗传统剂型的有前途的替代品。

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