Micro- and Nanoencapsulated Hybrid Delivery System (MNEHDS): A Novel Approach for Colon-Targeted Oral Delivery of Berberine

作者：Lingzhi Zhang, Mingyan Li, Guiqiu Zhang, Changxing Gao, Shengfang Wang, Tingting Zhang, Chen Ma, Lianyan Wang, Qing Zhu · 发表于：Molecular Pharmaceutics · 年份：2021 · DOI：10.1021/acs.molpharmaceut.0c00970 · 被引用次数：24 · 研究领域：Berberine and alkaloids research、Alkaloids: synthesis and pharmacology、Plant-based Medicinal Research

Berberine (BBR) is currently explored in the oral treatment of many disorders, especially in those involving inflammatory processes. Nanotechnology-based drug delivery systems are emerging as an effective approach for improving the poor oral absorption/bioavailability of BBR. To optimize the BBR immunoregulatory effects on a specific part of the gastrointestinal tract, here we describe a micro- and nanoencapsulated hybrid delivery system (MNEHDS) for colon-targeted oral delivery of BBR and test its therapeutic efficacy in a murine colitis model. The MNEHDS is formed by encapsulation of BBR-loaded poly(lactic- co -glycolic acid) nanoparticles into a pH-sensitive, BBR-pre-entrapped Eudragit FS30D matrix to form a hybrid microparticle composed of the BBR and BBR nanoparticles. Once in the colonic environment, the microencapsulated BBR is almost completely released for immediate action, while BBR nanoparticles can provide sustained release of BBR subsequent to their intestinal absorption. One dose of oral MNEHDS/BBR treatment results in significant attenuation of acute colitis induced by dextran sulfate sodium. The MNEHDS/BBR also proves to be effective during chronically induced colitis with two doses given 1 week apart. The improved efficacy is accompanied by decreased production of colon inflammation. Comparatively, oral treatment with one or two 7-day courses of free BBR has less effect on ameliorating either acute or chronic colitis. Thus, MNEHDS represents a novel delivery ...