Hamed Rania, Abu Alata Wala'a, Abu-Sini Mohammad, Abulebdah Dina H, Hammad Alaa M, Aburayya Rafa
Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, Jordan.
Gels. 2023 Jul 23;9(7):592. doi: 10.3390/gels9070592.
Nanoemulsions and bigels are biphasic delivery systems that can be used for topical applications. The aim of this study was to incorporate an oil-in-water ciprofloxacin hydrochloride nanoemulsion (CIP.HCl NE) into two types of bigels, Type I (oleogel (OL)-in-hydrogel (WH)) and Type II (WH-in-OL) to enhance drug penetration into skin and treat topical bacterial infections. Bigels were prepared at various ratios of OL and WH (1:1, 1:2, and 1:4). Initially, CIP.HCl NE was prepared and characterized in terms of droplet size, zeta potential, polydispersity index, morphology, and thermodynamic and chemical stability. Then CIP.HCl NE was dispersed into the OL or WH phase of the bigel. The primary physical stability studies showed that Type I bigels were physically stable, showing no phase separation. Whereas Type II bigels were physically unstable, hence excluded from the study. Type I bigels were subjected to microstructural, rheological, in vitro release, antimicrobial, and stability studies. The microscopic images showed a highly structured bigel network with nanoemulsion droplets dispersed within the bigel network. Additionally, bigels exhibited pseudoplastic flow and viscoelastic properties. A complete drug release was achieved after 4-5 h. The in vitro and ex vivo antimicrobial studies revealed that bigels exhibited antimicrobial activity against different bacterial strains. Moreover, stability studies showed that the rheological properties and physical and chemical stability varied based on the bigel composition over three months. Therefore, the physicochemical and rheological properties, drug release rate, and antimicrobial activity of Type I bigels could be modified by altering the OL to WH ratio and the phase in which the nanoemulsion dispersed in.
纳米乳剂和双凝胶是可用于局部应用的双相给药系统。本研究的目的是将水包油型盐酸环丙沙星纳米乳剂（CIP.HCl NE）加入到两种类型的双凝胶中，即I型（油凝胶（OL）包埋于水凝胶（WH）中）和II型（WH包埋于OL中），以增强药物透皮能力并治疗局部细菌感染。双凝胶以不同比例的OL和WH（1:1、1:2和1:4）制备。首先，制备CIP.HCl NE并对其进行表征，包括液滴大小、zeta电位、多分散指数、形态以及热力学和化学稳定性。然后将CIP.HCl NE分散到双凝胶的OL或WH相中。初步的物理稳定性研究表明，I型双凝胶在物理上是稳定的，未出现相分离。而II型双凝胶在物理上不稳定，因此被排除在研究之外。对I型双凝胶进行了微观结构、流变学、体外释放、抗菌和稳定性研究。微观图像显示出高度结构化的双凝胶网络，纳米乳剂液滴分散在双凝胶网络中。此外，双凝胶表现出假塑性流动和粘弹性。4至5小时后实现了药物的完全释放。体外和离体抗菌研究表明，双凝胶对不同细菌菌株具有抗菌活性。此外，稳定性研究表明，在三个月的时间里，流变学性质以及物理和化学稳定性会因双凝胶组成的不同而变化。因此，通过改变OL与WH的比例以及纳米乳剂分散所在的相，可以改变I型双凝胶的物理化学和流变学性质、药物释放速率以及抗菌活性。
