HPMA‐PEG Surfmers and Their Use in Stabilizing Fully Biodegradable Polymer Nanoparticles

Abstract

AbstractThe most adopted methods to produce polymer nanoparticles (NPs) for medical and pharmaceutical applications use surfactants that are toxic and physically adsorbed to the NPs, with the risk of desorption and insurgence of side effects. A valid alternative is represented by the use of surfmers, reactive surfactants that are chemically linked to the polymer chains, thus avoiding the release of toxic species. In this case, the lack of biodegradable surfmers introduces the concern of polymer accumulation into the body. In this work, biodegradable, poly(ethylene glycol) (PEG)ylated N‐(2‐hydroxypropyl) methacrylamide (HPMA) based surfmers are synthesized and used to stabilize lipophilic NPs. In particular, the NP core is made from a macromonomer comprising a poly(lactic acid) (PLA) chain functionalized with HPMA double bond. The NP forming polymer chains are then constituted by a uniform poly(HPMA) backbone that is biocompatible and water soluble and hydrolysable PEG and PLA pendants assuring the complete degradability of the polymer. The stability provided to these NPs by the synthesized surfmers is studied in the cases of both emulsion free radical polymerization and solution free radical polymerization followed by the flash nanoprecipitation of the obtained amphiphilic copolymers.