Jøraholmen May Wenche, Vanić Zeljka, Tho Ingunn, Skalko-Basnet Nataša
University of Tromsø, Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, Universitetsveien 57, Tromsø 9037, Norway.
University of Zagreb, Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, A. Kovačića 1, Zagreb 10000, Croatia.
Int J Pharm. 2014 Sep 10;472(1-2):94-101. doi: 10.1016/j.ijpharm.2014.06.016. Epub 2014 Jun 10.
The choice of drug therapy in pregnant patients suffering from vaginal infections is limited by the safety profile of the drug. Assuring the efficient topical therapy to avoid systemic absorption is considered the best therapy option. Chitosan-coated liposomes have been developed and optimized to assure localized therapy of clotrimazole. Chitosan was selected as mucoadhesive polymer both to prolong system's retention at the vaginal site and act on biofilms responsible for high recurrence of infections. Sonicated liposomes were coated with chitosan in three different concentrations, namely 0.1, 0.3 and 0.6% (w/v). Clotrimazole-containing (22 μg/mg lipid) chitosan-coated liposomes were in the size range of 100-200 nm. The in vitro release studies confirmed prolonged release of clotrimazole from both non-coated and chitosan-coated liposomes as compared to control. The ex vivo penetration experiments performed on the pregnant sheep vaginal tissue showed that coated liposomes assured increased clotrimazole tissue retention and reduced its penetration as compared to the control. Mucin studies revealed that the coating with lower chitosan concentration increased the system's mucoadhesive potential, as compared to coating with higher concentrations. These results provide a good platform for further in vivo animal studies on mucoadhesive liposomes destined to localized vaginal therapy.
患有阴道感染的孕妇的药物治疗选择受到药物安全性的限制。确保有效的局部治疗以避免全身吸收被认为是最佳治疗选择。已开发并优化了壳聚糖包衣脂质体，以确保克霉唑的局部治疗。选择壳聚糖作为粘膜粘附聚合物，既能延长系统在阴道部位的保留时间，又能作用于导致感染高复发率的生物膜。将超声处理的脂质体用三种不同浓度（即0.1%、0.3%和0.6%（w/v））的壳聚糖包衣。含克霉唑（22μg/mg脂质）的壳聚糖包衣脂质体大小在100-200nm范围内。体外释放研究证实，与对照相比，未包衣和壳聚糖包衣脂质体中的克霉唑释放时间延长。在怀孕绵羊阴道组织上进行的离体渗透实验表明，与对照相比，包衣脂质体可确保克霉唑在组织中的保留增加，其渗透减少。粘蛋白研究表明，与较高浓度包衣相比，较低壳聚糖浓度包衣可增加系统的粘膜粘附潜力。这些结果为进一步对用于局部阴道治疗的粘膜粘附脂质体进行体内动物研究提供了一个良好的平台。
