Department of Pharmacy, COMSATS University, Islamabad, Abbottabad Campus, 22010, Pakistan.
Department of Pharmacy, COMSATS University, Islamabad, Abbottabad Campus, 22010, Pakistan.
Int J Biol Macromol. 2022 Aug 31;215:579-595. doi: 10.1016/j.ijbiomac.2022.06.161. Epub 2022 Jun 29.
The biopolymers-based two-fold system could provide a sustained release platform for drug delivery to the brain resisting the mucociliary clearance, enzymatic degradation, bypassing the first-pass hepatic metabolism, and BBB thus providing superior bioavailability through intranasal administration. In this study, poloxamers PF-127/PF-68 grafted chitosan HCl-co-guar gum-based thermoresponsive hydrogel loaded with eletriptan hydrobromide laden pullulan nanoparticles was synthesized and subjected to dynamic light scattering, Fourier transform infrared spectroscopy, thermal analysis, x-ray diffraction, scanning electron microscopy, stability studies, mucoadhesive strength and time, gel strength, cloud point assessment, rheological assessment, ex-vivo permeation, cell viability assay, histology studies, and in-vivo Pharmacokinetics studies, etc. It is quite evident that CSG-EH-NPs T-Hgel has an enhanced sustained release drug profile where approximately 86 % and 84 % of drug released in phosphate buffer saline and simulated nasal fluid respectively throughout 48 h compared to EH-NPs where 99.44 % and 97.53 % of the drug was released in PBS and SNF for 8 h. In-vivo PKa parameters i.e., mean residence time (MRT) of 11.9 ± 0.83 compared to EH-NPs MRT of 10.2 ± 0.92 and area under the curve (AUC) of 42,540.5 ± 5314.14 comparing to AUC of EH-NPs 38,026 ± 6343.1 also establish the superiority of CSG-EH-NPs T-Hgel.
基于生物聚合物的双重系统可以为药物输送提供一个持续释放的平台，该系统可以抵抗黏液纤毛清除、酶降解、绕过首过肝代谢和 BBB，从而通过鼻腔给药提供卓越的生物利用度。在这项研究中，制备了载有埃利曲坦氢溴酸盐的普鲁兰纳米粒的泊洛沙姆 PF-127/PF-68 接枝壳聚糖 HCl-co-瓜尔胶基温敏水凝胶，并对其进行了动态光散射、傅里叶变换红外光谱、热分析、X 射线衍射、扫描电子显微镜、稳定性研究、黏膜附着力和时间、凝胶强度、浊点评估、流变学评估、体外渗透、细胞活力测定、组织学研究和体内药代动力学研究等。很明显，CSG-EH-NPs T-Hgel 具有增强的持续释放药物特性，与 EH-NPs 相比，在磷酸盐缓冲盐水和模拟鼻腔液中分别在 48 小时内释放了约 86%和 84%的药物，而 EH-NPs 在 PBS 和 SNF 中在 8 小时内释放了 99.44%和 97.53%的药物。体内 PKa 参数，即平均驻留时间（MRT）为 11.9±0.83，与 EH-NPs 的 MRT 为 10.2±0.92相比，以及 AUC 为 42,540.5±5314.14，与 EH-NPs 的 AUC 为 38,026±6343.1 相比，也证明了 CSG-EH-NPs T-Hgel 的优越性。
