INVERSE MINIEMULSION POLYMERIZATION OF PHOSPHATE-LOADED HYDROGEL NANOPARTICLES FOR SEPSIS PREVENTION

Drug delivery is an exciting field of interdisciplinary research that has captured the interests of the Pharmaceutical and Biotechnology industry. With the continual advances in discovery and synthesis of effective drugs, it is imperative to create safe and efficient drug-delivery systems. Biocompatible polymer nanoparticles are beginning to provide innovative solutions and form the frontier of advanced drug-delivery technology and Nanomedicine. Phosphate ions have been identified to be instrumental in healing wounds and preventing post-surgery gut-derived sepsis. We have developed a process of inverse miniemulsion polymerization to produce highly crosslinked, Biocompatible PEG diacrylate nanoparticles in the size range of 156-217 nm encapsulated with comprising phosphate ions. An aqueous solution containing high amounts of crosslinker (PEG diacrylate 575), NVP, phosphate salt and a water-soluble thermal initiator was emulsified in cyclohexane (oil-phase) by the application of high shear (ultrasound) to generate an inverse miniemulsion. The aqueous nano-droplets were stabilized against coalescence by the use for two non-ionic surfactants. The presence of phosphate salt within these stable nano-droplets prevented destabilization of the miniemulsion against Ostwald ripening. The encapsulation of phosphate within the nanoparticles is made certain by selecting a phosphate concentration dictated by the PEGDA-Phosphate temperature-dependent thermodynamics. Reported experimental measurements include monomer conversion, particle size measurement and aqueous swelling characteristics. Nanoparticle tracking Analysis (NTA) methodology developed by Nanosight Inc. was used for particle size measurements. A factorial design of experimentation coupled with the application of a xiii kinetic model indicate a low range (10-3 – 10-4) of the initiator efficiency in the reaction kinetics. The comparison of experimental conversion data with model predictions, points towards a well documented notion of a drastic reduction in initiator efficiency that once a critical degree of crosslinking is achieved within the nanoparticles during the reaction. The inverse swelling ratios (proportional to crosslink density) of the nanoparticles tend to substantiate the above kinetic behavior. The preliminary medical testing of the synthesized nanoparticles showed promising results indicating the efficacy of this strategy in drug delivery and regenerative tissue engineering.M.S. in Chemical Engineering, May 201