Novel design of amphiphilic nanogels through the crosslinking of polymeric micelle matrix by means of metallic cations

Polymeric nanogels are crosslinked polymeric networks composed of hydrophilic or amphiphilic polymers that self-assemble in aqueous environment and are crosslinked either with physical (e.g., hydrophobic and electrostatic interactions) or chemical bonds. Their unique properties have drawn attention in the drug delivery field due to the high loading capacity, triggered response, biocompatibility and surface functionality. However, since nanogels are swollen polymeric matrixes, they usually have good loading capacity for hydrophilic biomolecules and less for small hydrophilic molecules and cargos that resemble about 70% of the marketed drugs according to the biopharmaceutics classification system. In this study, we present a novel approach to produce amphiphilic nanogels based on the modification of polymeric micelle (PM)-forming-poly(ethylene oxide)-b-poly(propylene oxide) (PEO-PPO) block copolymers with terpyridine (TP) ligands that can form a coordinative bond with zinc ions. The amphiphilic domains of the nanogels are expected to encapsulate the cargo the hydrophilic ones to stabilize the structure of the nanoparticle and display photoluminescence properties originated from the TP-Zn²⁺ complex. The formation of the TP-modified block copolymer was characterized by ¹H-NMR and FTIR. Physical stability over time and upon dilution of the nanogels was measured using dynamic light scattering (DLS), and their morphology by high resolution-scanning electron microscopy (HR-SEM). The photoluminescence properties were confirmed by fluorescence spectrophotometry. Cell viability was evaluated in a model of intestinal epithelium, Caco2 cell line. Finally, encapsulation and release of efavirenz as model hydrophobic drug was assessed.