Micro- and Nanoencapsulated Hybrid Delivery System (MNEHDS): A Novel Approach for Colon-Targeted Oral Delivery of Berberine
Micro- and Nanoencapsulated Hybrid Delivery System (MNEHDS): A Novel Approach for Colon-Targeted Oral Delivery of Berberine
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微米和纳米封装混合递送系统（MNEHDS）：一种结肠靶向口服小檗碱的新方法
DOI：
10.1021/acs.molpharmaceut.0c00970
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发表时间：
2021
影响因子：
4.9
通讯作者：
Qing Zhu
中科院分区：
文献类型：
--
作者：
Lingzhi Zhang;Mingyan Li;Guiqiu Zhang;Changxing Gao;Shengfang Wang;Tingting Zhang;Chen Ma;Lianyan Wang;Qing Zhu
小檗碱（BBR）目前正在探索许多疾病的口服治疗，特别是在那些涉及炎症过程。基于纳米技术的药物递送系统正在成为改善BBR口服吸收/生物利用度差的有效方法。为了优化BBR对胃肠道特定部分的免疫调节作用，在这里，我们描述了一种用于结肠靶向口服BBR的微囊和纳米囊化混合递送系统（MNEHDS），并在小鼠结肠炎模型中测试其治疗效果。MNEHDS通过将BBR负载的聚（乳酸-共-乙醇酸）纳米颗粒包封到pH敏感的BBR预包埋的Eudragit FS 30 D基质中以形成由BBR和BBR纳米颗粒组成的混合微粒来形成。一旦在结肠环境中，微囊化的BBR几乎完全释放以立即起作用，而BBR纳米颗粒可以在它们的肠吸收之后提供BBR的持续释放。一剂口服MNEHDS/BBR治疗导致葡聚糖硫酸钠诱导的急性结肠炎显著减弱。MNEHDS/BBR也被证明在慢性诱导的结肠炎期间有效，两次给药间隔1周。改善的功效伴随着结肠炎症的产生减少。相比之下，口服一次或两次7天疗程的游离BBR对改善急性或慢性结肠炎的作用较小。因此，MNEHDS代表了BBR和潜在的其他治疗剂的新型递送系统，以治疗炎症性肠病。
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 system for BBR, and potentially other therapeutic agents, to treat inflammatory bowel disease.