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连接斑和连接小体:一种新型的囊泡和胶束系统,可增强难溶性药物的口服递送:体外特性和体内性能的优化。

Desosomes and desimicelles - a novel vesicular and micellar system for enhanced oral delivery of poorly soluble drug: Optimization of in vitro characteristics and in vivo performance.

机构信息

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt.

Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo 12622, Egypt.

出版信息

Eur J Pharm Biopharm. 2024 Jul;200:114324. doi: 10.1016/j.ejpb.2024.114324. Epub 2024 May 15.

DOI:10.1016/j.ejpb.2024.114324
PMID:38759898
Abstract

This study introduces two innovative nanocarrier systems to improve oral drug delivery. Desosomes and desimicelles combine Deep eutectic solvent (DES) with vesicular or micellar nanosystems, respectively. These novel nanosystems integrate the DES solubilization potency for administering drugs with low aqueous solubility and the vesicular and micellar systems to bypass physiological barriers and improve poor drug bioavailability. Lornoxicam (LRX) is a BCS class II anti-inflammatory with limited aqueous solubility and rapid clearance. Desosomes and desimicelles were prepared and successfully optimized. The optimization depended on particle size, zetapotential, entrapment efficiency, and solubility. The optimized desosomes (LRX-DES-V) and desimicelles (LRX-DES-M) were pictured by transmission electron microscope. Differential scanning calorimetry (DSC) and FTIR analysis indicated the successful inclusion of LRX inside each system. Invitro LRX release profiles revealed controlled release of LRX-DES-V and LRX-DES-M, with more sustained release by the later one. In-vivo study, inflammation was induced using a carrageenan rat model, and the anti-inflammatory effect of LRX-pure, marketed product, traditional niosomes, LRX-DES-V & LRX-DES-M were determined using inhibition %, serum inflammatory cytokines, and histopathology. After 4 h of induction, LRX-DES-M (68.05%) showed a significant inhibition compared to LRX-DES-V (63.57%). LRX-DES-M also showed a better reduction in COX2, PGE2, and TNF-α (1.25-fold, 1.24-fold, and 1.36-fold inhibition), respectively, compared to LRX-DES-V. We can conclude that LRX-DES-V and LRX-DES-M showed better effects than all other groups and that LRX-DES-M might be more effective than LRX-DES-V.

摘要

本研究介绍了两种创新的纳米载体系统,以改善口服药物传递。Desosomes 和 desimicelles 分别将深共晶溶剂 (DES) 与囊泡或胶束纳米系统结合。这些新型纳米系统将 DES 的增溶能力集成到给药系统中,用于管理低水溶性药物,同时利用囊泡和胶束系统来绕过生理屏障并提高药物生物利用度差的问题。洛索洛芬(LRX)是一种 BCS 类 II 抗炎药,水溶性有限,清除率快。制备并成功优化了 Desosomes 和 desimicelles。优化取决于粒径、Zeta 电位、包封效率和溶解度。通过透射电子显微镜对优化后的 Desosomes(LRX-DES-V)和 Desimicelles(LRX-DES-M)进行了成像。差示扫描量热法(DSC)和傅里叶变换红外分析(FTIR)表明 LRX 成功地包含在每个系统中。体外 LRX 释放曲线显示 LRX-DES-V 和 LRX-DES-M 的控释,后者具有更持续的释放。在体内研究中,使用角叉菜胶大鼠模型诱导炎症,并使用抑制%、血清炎症细胞因子和组织病理学来确定 LRX-纯品、市售产品、传统的尼奥斯omes、LRX-DES-V 和 LRX-DES-M 的抗炎效果。在诱导 4 小时后,LRX-DES-M(68.05%)与 LRX-DES-V(63.57%)相比显示出显著的抑制作用。与 LRX-DES-V 相比,LRX-DES-M 还显示出对 COX2、PGE2 和 TNF-α 的更好降低(抑制作用分别为 1.25 倍、1.24 倍和 1.36 倍)。我们可以得出结论,LRX-DES-V 和 LRX-DES-M 比所有其他组表现出更好的效果,而 LRX-DES-M 可能比 LRX-DES-V 更有效。

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