Development and Evaluation of Letrozole-Loaded Hyaluronic Acid/Chitosan-Coated Poly(d,l-lactide-co-glycolide) Nanoparticles

Purpose Letrozole (LTZ), an aromatase inhibitor with poor aqueous solubility, is used as the first line treatment for hormonal sensitive breast cancer in postmenopausal women. The purpose of the current study is to develop hyaluronic acid (HA)/chitosan (Cs)-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for the delivery of LTZ to improve therapeutic efficacy, control release and minimize side effects of LTZ. Methods PLGA nanoparticles were prepared, and the effect of various parameters on particle size, surface charge, and encapsulation efficiency was extensively studied. The morphology of nanoparticles was visualized using transmission electron microscopy (TEM), and drug-polymer interactions were studied using differential scanning calorimetry (DSC) and Fourier transform-infrared spectroscopy (FT-IR). The in vitro release kinetics and effect of freeze-drying process on the physicochemical characteristics of nanoparticles were also evaluated. Moreover, the in vivo acute toxicities of blank and drug-loaded nanoparticles were assessed. Results PLGA nanoparticles exhibited nanosized (464.3 +/- 2.1 nm) spherical particles, negative surface charge (zeta-potential of - 10.5 +/- 0.4 mV), and high drug encapsulation efficiency of 63.9 +/- 3.7% and sustained drug release pattern over 48 h. The in vivo acute toxicity study revealed that the nanoparticles were well tolerated at a dose of 300 mg/kg. Conclusion HA/Cs-coated PLGA nanoparticles might provide a promising system for LTZ delivery and further investigations could confirm their potential efficacy in breast cancer therapy.