Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, Egypt.
Int J Nanomedicine. 2022 Aug 10;17:3543-3560. doi: 10.2147/IJN.S370235. eCollection 2022.
The aim of this work was to probe cubosomes for enhanced intestinal absorption and oral bioavailability of poorly absorbable fexofenadine HCl (FEX-HCl).
Two cubosomal systems were fabricated utilizing glyceryl mono-oleate, a lyotropic mono lamellar lipid as oil phase and poloxamer407 as stabilizer at weight ratios of 8:2 and 7:3. The morphology of cubosomes was researched using transmission electron microscopy (TEM) and particle size was measured using photon correlation spectroscopy. FEX-HCl release was monitored in vitro. The effect of cubosomal encapsulation on intestinal absorption was assessed using in situ rabbit intestinal perfusion technique. Carrageenan induced rat paw edema model was utilized to monitor in vivo anti-inflammatory effect before and after cubosomal encapsulation.
TEM revealed the existence of spherical and polygonal nanostructures arranged in honeycomb organization. Size measurement reflected nanoparticles with reduced size at higher poloxamer concentration. Release studies revealed liberation of FEX-HCl from cubosomes based on Higuchi kinetics model. The intestinal permeability data indicated incomplete absorption of FEX-HCl from simple aqueous solution with P-glycoprotein efflux contributing to this poor intestinal absorption. Incorporation of FEX-HCl in cubosomes enhanced membrane transport parameters. The intestinal absorption did not correlate with drug release suggesting that drug release is not the rate limiting with possible intact cubosomal transport. Cubosomal encapsulation of FEX-HCl significantly enhanced its in vivo anti-inflammatory efficacy compared to the aqueous FEX-HCl dispersion.
Cubosomes are promising novel carriers for enhancing intestinal absorption of FEX-HCl. Intact FEX-HCl-cubosomal absorption is possible via trans-lymphatic pathway but this requires further investigations.
本研究旨在探究立方液晶纳米载体（Cubosomes）对脂溶性差的盐酸非索非那定（FEX-HCl）的肠道吸收和口服生物利用度的增强作用。
采用甘油单油酸酯（一种溶致性单层脂质）作为油相，泊洛沙姆 407 作为稳定剂，按 8:2 和 7:3 的重量比制备两种立方液晶纳米载体系统。采用透射电子显微镜（TEM）研究立方液晶纳米载体的形态，并用光子相关光谱法测量粒径。体外监测 FEX-HCl 的释放情况。采用原位兔肠灌流技术评估立方液晶纳米载体包封对肠道吸收的影响。利用角叉菜胶诱导的大鼠足肿胀模型，监测立方液晶纳米载体包封前后的体内抗炎作用。
TEM 显示存在排列成蜂窝状的球形和多边形纳米结构。粒径测量结果表明，在较高的泊洛沙姆浓度下，粒径减小。释放研究表明，FEX-HCl 从立方液晶纳米载体中以 Higuchi 动力学模型释放。肠道通透性数据表明，FEX-HCl 从简单的水溶液中不完全吸收，P-糖蛋白外排是导致这种肠道吸收不良的原因。将 FEX-HCl 包封在立方液晶纳米载体中可增强膜转运参数。肠道吸收与药物释放不相关，提示药物释放不是限速步骤，可能是完整的立方液晶载体转运。与 FEX-HCl 的水溶液分散体相比，FEX-HCl 的立方液晶纳米载体包封显著增强了其体内抗炎效果。
立方液晶纳米载体是增强 FEX-HCl 肠道吸收的有前途的新型载体。FEX-HCl 立方液晶纳米载体的完整吸收可能通过肠淋巴途径实现，但这需要进一步研究。
