Multiple strategies to produce lipophilic nanoparticles leaving water-soluble poly(HPMA)

Abstract

N-(2-Hydroxypropyl) methacrylamide (HPMA) can be used to produce water-soluble polymers with non-immumogenic properties that are widely used in drug delivery applications. In this study, an HPMA modification was proposed, which leads to lipophilic nanoparticle (NP) production. Ring opening polymerization of HPMA with lactide (LT) was performed to obtain reactive HPMA-LA_n macromonomers with different average chain lengths. The HPMA modification produced lipophilic macromonomer starting materials that were subsequently used to obtain polymer nanoparticles that are suitable for drug delivery applications of hydrophobic drugs. Different strategies were explored. First, emulsion-free radical polymerization was conducted to obtain the monodispersed PEGylated polymer NPs. Next, solvent polymerization was performed to produce a poly(HPMA-LA_n)-based polymer solution, which was used to produce the NPs via flash nanoprecipitation. Because these NPs are designed for drug delivery applications, their fast degradability in a biological medium was verified. Additionally, the ability to load and release a drug (i.e., dexamethasone) was verified for the NPs, which were synthesized using the proposed strategies, to demonstrate the effectiveness of the HPMA functionalization to obtain a system for delivering lipophilic drugs.