Synthesis of Polyphosphate-Loaded Nanoparticles Using Inverse Miniemulsion Polymerization for Sustained Delivery to the Gastrointestinal Tract

Macromol React Eng. 2019 Apr;13(2):1800068. doi: 10.1002/mren.201800068. Epub 2019 Feb 18.

Abstract

Polyphosphate salts, such as sodium hexametaphosphate (PPi), are effective in the attenuation of collagenase and biofilm production and prevention of anastomotic leak in mice models. However, systemic administration of polyphosphate solutions to the gut presents a series of difficulties such as uncontrolled delivery to target and off-site tissues. In this article a process to produce PPi-loaded poly(ethylene glycol) diacrylate (PEGDA) hydrogel nanoparticles through miniemulsion polymerization is developed. The effects of using a polyphosphate salt, as compared to a monophosphate salt, is investigated through cloud point measurements, which is then translated to a change in the required HLB of the miniemulsion system. A parametric study is developed and yields a way to control particle swelling ratio and mean diameter based on the surfactant and/or initiator concentration, among other parameters. Finally, release kinetics of two different crosslink density particles shows a sustained and tunable release of the encapsulated polyphosphate.

Keywords: drug delivery; hydrogel nanoparticles; miniemulsion polymerization; phosphate salts; polymerization reaction engineering.