pH- and thermoresponsive amphiphilic terpolymers: Synthesis and formulation of drug-loaded nanomicelles

Introduction
Smart polymers that change their structural conformation upon external stimuli have emerged as candidates for the formulation of multi-responsive nanocarriers. Development of such nanoplatforms is crucial for bypassing body resistance mechanisms in targeted drug or gene delivery applications.
Methods
In this work, reversible addition–fragmentation chain transfer (RAFT) polymerization led to the synthesis of a series of poly(2-(diisopropylamino)ethyl methacrylate-co-2-(dimethylamino)ethyl methacrylate-co-oligoethylene glycol methyl ether methacrylate), P(DIPAEMA-co-DMAEMA-co-OEGMA) terpolymers. Molecular characterization and self-assembly of polymers in various aqueous environments were carried out. The organic co-solvent protocol was followed for the drug loading of curcumin and quercetin in polymeric micelles. Physicochemical and photophysical properties of loaded nanoparticles were evaluated for a period of three weeks.
Results
P(DIPAEMA-co-DMAEMA-co-OEGMA) terpolymers were successfully synthesized, presenting different pH responses at pH values of 3, 7, and 10 in terms of mass and size of the self-assembled copolymer structures. Temperature-dependent dynamic light scattering (DLS) experiments revealed the thermoresponsive properties of the copolymer micellar aggregates. Curcumin and quercetin were efficiently encapsulated within the micelles, presenting colloidal stability as measured by DLS and ultraviolet–visible absorption spectroscopy (UV-Vis). Fluorescence experiments resulted in enhanced and red-shifted spectra for curcumin-loaded nanoparticles compared to pure curcumin. Quercetin-loaded ones also exhibited an enhancement in aggregation characteristics.
Conclusions
Multi-responsive and stable nanocarriers were fabricated, showcasing the applicability of P(DIPAEMA-co-DMAEMA-co-OEGMA) terpolymers in biomedicine.