(238b) A Scalable Gold Nanoparticle-Templating Method for Generating Erodible Drug Microparticles without Use of Exogenous Biodegradable Polymers

Bile acids and other soluble salts are proposed as therapeutic agents for various diseases, including bile synthesis disorders, liver diseases, osteoarthritis and cancer. However, oral or subcutaneous administration of a solubilized version of these drugs have limited efficacy and impose unwanted side effects. Here, we describe a gold-templating method for fabricating stable, particle drug – cholate or deoxycholate – microparticles. The reduction of gold ions at the oil-water interface in a double emulsion solvent evaporation process enables a gold-bile salt interaction, leading to the formation of bile salt particles. We demonstrate that the size of the particles was linked to the bile salt concentration in the water phase, and the resulting composite microparticles release active salts into solution via a surface erosion process. Importantly, we illustrate these bile salts particles’ capability to lyse adipocytes, both in vitro and in vivo, with minimal side effects contrary to the FDA approved salt solution that leads to severe inflammation and ulceration. Finally, we show that the gold-nanoparticle templating particle fabrication approach can be extend to a variety of soluble drugs, and the resulting salt-based particles can be loaded with other small molecule drugs, using rhodamine as a model, allowing for co-administration of the released bile salt with other therapeutic agents. Overall, particle-based salt drugs open opportunities for localized delivery of these salts, improving efficacy while avoiding adverse side effects associated with high doses, multiple treatments, and the use of exogenous biodegradable polymers.

Fig 1. Composite Metal-Nanoparticle Templated Particles. (A) Degradation of cholate particles via surface erosion over 4 weeks (scale bar=1 mm); (B) Release of cholate from composite particles; (C) (left to right) Structure of cholic acid, deoxycholic acid, and chenodeoxycholic acid, and their associated particles (scale bars=1 mm); (D) Fluorescently loaded cholate particles (scale bar=10 mm).