Development and characterization of an injectable thermoresponsive PLGA nanoparticle-loaded in situ gel for sustained exemestane delivery.

INTRODUCTION

The present study aimed to develop and evaluate a thermoresponsive in situ gel incorporating Exemestane-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles for sustained drug delivery.

METHODS

Exemestane-loaded PLGA nanoparticles were prepared by nanoprecipitation and characterised for particle size, zeta potential, morphology, entrapment efficiency, and drug release behaviour.

RESULTS

The nanoparticle exhibited a mean particle size of 257.6 nm, moderate stability with a zeta potential of-15.3mV, high encapsulation efficiency (93.46± 2.46%) and drug loading 27.8±1.2% (0.278±0.012mg Exemestane /mg nanoparticles), indicating successful formulation. The optimised nanoparticles were incorporated into a poloxamer-based thermoresponsive in situ gel system modified with chitosan to enhance gel strength and bioadhesion. The formulation was optimised using a Box-Behnken design, achieving a gelation temperature of 38.3±0.5 °C and gelation time of 0.75±0.5 min, suitable for physiological conditions. In vitro drug release studies demonstrated a sustained release profile with minimal burst effect, achieving approximately 80% drug release over 24 hours. Release kinetics followed the Korsmeyer-Peppas model, indicating an Fickian and diffusion mechanism governed by both diffusion and polymer erosion.The formulation exhibited desirable physicochemical properties, appropriate rheological behaviour, controlled gel erosion, and stability over three months.Ex vivo and HET-CAM studies indicated reduced angiogenesis, suggesting potential therapeutic efficacy in breast cancer treatment.

DISCUSSION: Overall, the developed nanoparticle-loaded thermoresponsive in situ gel represents a promising localised sustained drug delivery platform for Exemestane and warrants further evaluation in appropriate cellular and in vivo breast cancer models.