用于口服给药的姜黄素负载胆盐稳定纳米囊泡的体内和体外评估。

In-vivo and in-vitro assessment of curcumin loaded bile salt stabilized nanovesicles for oral delivery.

作者信息

Hashem Fahima M, Elkhateeb Dalia, Ali Marwa M, Abdel-Rashid Rania S

机构信息

Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, POB 11795, Egypt.

Central Administration of Drug Control, Egyptian Drug Authority, Cairo, Egypt.

出版信息

Daru. 2024 Dec 23;33(1):9. doi: 10.1007/s40199-024-00544-9.

DOI:10.1007/s40199-024-00544-9

PMID:39714544

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11666894/

Abstract

BACKGROUND

Bile salts enriched nanovesicles (bilosomes) have been attention worthy in the past few years due to their distinctive effect on the enhancement of drug delivery through various physiological administration routes. Oral delivery of multifunctioning phytochemical curcumin has faced a lot of difficulties due to its scarce solubility and poor oral bioavailability.

OBJECTIVE

The current investigation aimed to develop curcumin loaded bilosomes for improvement of oral curcumin bioavailability with maximum efficiency and safety.

METHODS

The effect of formulation variables (type of span, SDC % to total lipid content Span/Cholesterol molar ratio) on physicochemical characterization and in vitro drug release in simulated intestinal fluid was investigated. Furthermore, in-vivo protective effect of bilosomes on hepatic and renal functions was also studied.

RESULTS

and conclusion. The results revealed that the best curcumin loaded bilosomal formulation showed spherical nanovesicular morphology with particle size 145.1 ± 19.42 nm with highly reasonable %EE (93%), Zeta potential (≥ -30mv), prominent controlled in-vitro release reaching 55.18 ± 1.10 after 96 h. The formulation also showed good storage stability with negligible differences in physical features and content. The IC50 values of bilosomal, niosomal, and free curcumin were 216.50, 211.44, and 121.63 mmol/ml, respectively revealing that the unencapsulated curcumin displayed high toxicity on Caco2 cell line (nearly 2 folds). Additionally, the prepared bilosomes showed significant in-vivo hepatic and renal protection in liver cirrhosis induced rats with conservation to all liver and renal markers and histopathological morphology. The study assumes the effectiveness and safety of oral delivery of curcumin loaded bile salts stabilized nanovesicles and its powerful commandment for further investigations.

摘要

背景

富含胆盐的纳米囊泡（脂质体）在过去几年中备受关注，因为它们通过各种生理给药途径对增强药物递送具有独特作用。多功能植物化学物质姜黄素的口服给药由于其溶解度低和口服生物利用度差而面临诸多困难。

目的

本研究旨在开发载姜黄素脂质体，以最高效率和安全性提高姜黄素的口服生物利用度。

方法

研究了配方变量（司盘类型、胆盐脱氧胆酸钠占总脂质含量的百分比、司盘/胆固醇摩尔比）对物理化学特性以及在模拟肠液中的体外药物释放的影响。此外，还研究了脂质体对肝肾功能的体内保护作用。

结果与结论。结果显示，最佳的载姜黄素脂质体制剂呈现球形纳米囊泡形态，粒径为145.1±19.42 nm，包封率（%EE）非常合理（93%），zeta电位（≥ -30mv），体外释放显著可控，96小时后达到55.18±1.10。该制剂还显示出良好的储存稳定性，物理特性和含量差异可忽略不计。脂质体、非离子型脂质体和游离姜黄素的IC50值分别为216.50、211.44和121.63 mmol/ml，表明未包封的姜黄素对Caco2细胞系具有高毒性（近2倍）。此外，制备的脂质体在肝硬化诱导的大鼠中显示出显著的体内肝和肾保护作用，所有肝和肾标志物以及组织病理学形态均得以保留。该研究认为口服载姜黄素胆盐稳定纳米囊泡是有效且安全的，并且强烈建议进一步研究。