Poly(lactic-co-glycolic) acid nanoparticles with thermoresponsive shell for sustained release of dexamethasone

Abstract

Polymeric nanocarriers based on poly(lactide-co-glycolide) (PLGA) enable drug encapsulation while achieving increased solubility of hydrophobic drugs, enhanced plasmatic half-life, and protecting the drug from early degradation/metabolization. Nevertheless, it is still difficult to effectively regulate the drug release from nanocarriers. Covering the surface of PLGA nanoparticles (NPs) with a thermoresponsive shell may be the key factor for building drug delivery systems with temporal and spatial control. In this respect, PLGA NPs with a mean size of 212 nm, containing dexamethasone (Dex) (Dex/PLGA NPs) have been produced by the dialysis technique without the use of a surfactant. Then, the nanoparticles were covered with poly(N-isopropylacrylamide-co-4-vinyl pyridine) (PVP) by ionic interactions between the amine groups of the PVP and carboxylic groups of PLGA. FT-IR and XPS spectroscopy were used to identify the new functional groups introduced on the PLGA nanoparticles' surface. The assembly of PVP on the PLGA NPs was analyzed by monitoring the particle size with temperature, zeta potential, AFM, and TEM analysis. The in vitro drug delivery investigation showed that temperature has significant control over the release rate of Dex from PVP-coated PLGA NPs. The thermosensitive polymer is hydrated at temperatures lower than LCST (20 °C) and forms a gel around the nanoparticles slowing down the release rate of Dex. Above the LCST, PVP becomes hydrophobic, collapses, inducing a substantially slower and sustained release of Dex, with 84 % released at 200 h.