Phosphate‐Loaded Hydrogel Nanoparticles for Sepsis Prevention Prepared via Inverse Miniemulsion Polymerization

Abstract

Local depletion of intestinal phosphate triggers changes in bacterial phenotypes that adversely affect the health of the host. This article describes a process for encapsulating phosphates in crosslinked poly(ethylene glycol) diacrylate (PEGDA) nanoparticles using inverse miniemulsion polymerization as a drug delivery approach for sustained release of phosphates to the intestinal epithelium. The effects of crosslinker, PEGDA co‐monomer, N‐vinyl pyrrolidone, (NVP) and surfactant concentrations on the nanoparticle size distribution, swelling ratio and monomer conversion are investigated. Increased surfactant and PEGDA concentrations result in smaller particle size and swelling ratio. A copolymerization model of crosslinking is used to predict conversion and gelation dynamics as a function of polymerization conditions. The model assumes that bulk polymerization can be used to approximate inverse miniemulsion polymerization with an aqueous‐phase initiator. The initiator efficiency is used as an adjustable parameter to simulate the conversion dynamics, thus accounting for radical confinement effects and interaction with emulsifier molecules.

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

“…In previous studies, we have successfully prepared Pi‐loaded nanoparticles using a 0.086 m concentration of Pi . Figure b shows that the measured cloud point at these conditions is approximately 93 °C, which is almost thirty degrees higher than the reactor operating temperature of approximately 64 °C.…”

“…Equation shows how to calculate the HLB of our specific system. Based on previous experimentation and on literature considerations, we have established the required HLB for the Pi‐loaded miniemulsion to be approximately 5. However, after such a strong effect was seen in the cloud point of Tween 20 when switching from Pi to PPi, one could assume that the required HLB of our emulsion system might have been affected as well.…”

“…To this solution, varying amounts of the aqueous phase surfactant Tween 20 and of different azo‐type initiators were added depending on the desired formulation. Previous studies in the group have used potassium persulfate (KPS) as the initiator for producing hydrogel nanoparticles . However, recent studies have shown that KPS is not effective in initiating aqueous‐phase solutions of NVP and various literature studies stated that a water‐soluble azo‐initiators are more recommended for these types of applications.…”

“…Controlled delivery of therapeutics from nanoparticles provides a promising approach for maintaining a phosphate‐rich environment required for attenuation of bacterial phenotypes that complicate healing, such as collagenase and virulence expression. Our group has focused on the production of nanoparticles composed of a polyethylene glycol diacrylate (PEGDA)–n‐vinyl pyrrolidone (NVP) crosslinked hydrogel matrix encapsulated with phosphate salts and synthesized using an inverse miniemulsion polymerization process . Polyethylene glycol (PEG)‐coated nanoparticles, or PEGylated nanoparticles have demonstrated significant promise in drug delivery research as their surface does not promote non‐specific tissue binding while allowing for deeper penetration and longer circulation times especially in mucosal tissues .…”

“…In previous studies we have developed and tested several variants of phosphate‐loaded PEG hydrogel nanoparticles (NP). Specifically, we have studied two formulations, one using a monophosphate salt, potassium phosphate monobasic (NP‐Pi), and another with a polyphosphate salt that was proven more efficient in vitro, sodium hexametaphosphate (NP‐PPi). As the NP‐Pi particles were tested and characterized, they showed good encapsulation of the phosphate salt and a slow and controlled phosphate release over time.…”