Safari Hanieh, Kaczorowski Nicholas, Felder Michael L, Brannon Emma R, Varghese Mita, Singer Kanakadurga, Eniola-Adefeso Omolola
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Sci Adv. 2020 Dec 4;6(49). doi: 10.1126/sciadv.abd8019. Print 2020 Dec.
Bile acids are proposed as therapeutic agents for various diseases, including liver diseases and obesity. However, oral or subcutaneous administration of a solubilized version of these drugs has limited efficacy and imposes unwanted side effects. Here, we describe a gold-templating method for fabricating stable, bile salt-cholate or deoxycholate-microparticles. The gold ions' reduction at the oil-water interface in a double emulsion solvent evaporation process enables a gold-bile salt interaction and the formation of bile salt particles. We demonstrate that composite microparticles release cholate/deoxycholate into solution via a surface erosion process. We illustrate these particles' capability to lyse adipocytes, both in vitro and in vivo, with minimal side effects, contrary to the Food and Drug Administration-approved salt solution that leads to severe inflammation and ulceration. Overall, particle-based cholate/deoxycholate opens opportunities for localized delivery of these salts, improving efficacy while minimizing side effects associated with oral and subcutaneous use.
胆汁酸被认为是治疗包括肝脏疾病和肥胖症在内的各种疾病的药物。然而，口服或皮下注射这些药物的溶解形式疗效有限，并会产生不良副作用。在此，我们描述了一种用于制备稳定的胆盐 - 胆酸或脱氧胆酸微粒的金模板法。在双乳液溶剂蒸发过程中，油 - 水界面处金离子的还原实现了金 - 胆盐相互作用并形成胆盐颗粒。我们证明复合微粒通过表面侵蚀过程将胆酸/脱氧胆酸释放到溶液中。我们表明这些颗粒在体外和体内均具有裂解脂肪细胞的能力，且副作用最小，这与美国食品药品监督管理局批准的盐溶液相反，后者会导致严重炎症和溃疡。总体而言，基于颗粒的胆酸/脱氧胆酸为这些盐的局部递送提供了机会，在提高疗效的同时将与口服和皮下使用相关的副作用降至最低。
