Biodegradable, bile salt microparticles for localized fat dissolution.

Hanieh Safari,Mita Varghese,Nicholas Kaczorowski,Omolola Eniola-Adefeso,Emma R Brannon,Michael L Felder,Kanakadurga Singer

doi:10.1126/sciadv.abd8019

Abstract

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.

Highlights

Bile salts are naturally occurring surfactants that help solubilize lipids in the small intestine and regulate several hepatic, biliary, and intestinal functions [1, 2]
Bile salts are used as therapeutics to treat many diseases, including bile synthesis and liver disorders, cancer, and the reduction in undesired fat [4, 8, 9]
The composite particles degraded via surface erosion and released bile salts into solutions in a near-linear fashion, making them suitable for use as a controlled-release system in applications where limited efficacy and side effects have restricted the usage of bile salts

Summary

Introduction

Bile salts are naturally occurring surfactants that help solubilize lipids in the small intestine and regulate several hepatic, biliary, and intestinal functions [1, 2] Bile acids and their salts have been proposed as therapeutic agents for the treatment of different conditions, including bile synthesis and peroxisomal disorders [3, 4], primary biliary cirrhosis [5], gallstones and bile duct stones [1, 6], nonalcoholic fatty liver disease [7], type 2 diabetes [7], cancer [8, 9], and for local removal of undesired fat [10]. The associated inflammation and bruising and the required multiple dosages have waned the excitement for the use of Kybella and limited its application to submental fat reduction [10]

Methods

Results

Conclusion