Development of a Nanoparticle-Gel Microparticle Drug Delivery Vehicle for Lung Cancer Treatment

Abstract

A drug delivery system for the targeted treatment of lung cancer has previously been developed by Prud’homme et al. consisting of drug-loaded nanoparticles (NPs) polymerized into a PEG-based gel microparticle (GMP) network. Complications during the GMP polymerization process, however, have resulted in the uneven distribution and exclusion of NPs. In order to circumvent this issue and maximize drug loading in GMPs, a modification of the system has been proposed whereby GMPs are comprised entirely of crosslinked NPs. This study establishes the feasibility of forming a gel network out of NPs alone by either the Michael addition reaction or the highly stable copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), an important first step in the development of this system. Michael addition gels were made both by crosslinking a single type of functionalized nanoparticles and by reacting two differentially functionalized types of NPs. Both of these gels featured too high rates of degradation for practical use, however, likely due to a nucleophilic attack of hydroxide ions and unreacted amines on the ester groups of the linkage. CuAAC gels initially failed to form due to poor reaction kinetics as controlled by chain dynamics, and an increase in temperature alone was found insufficient to achieve gelling. A decrease in NP size from 130 nm to 80 nm, however, proved effective for gel formation.