Aim: Formulation and evaluation of anastrozole, an anti-cancer drug loaded in different biodegradable polymeric nanoparticles.
Materials and methods: Different carrier systems such as poly(lactide-co-glycolide) (PLGA 50:50), poly(lactic-acid) (PLA) and poly(ε-caprolactone) (PCL) are used to prepare nanoparticles by simple emulsion technique. The surfactants polyvinyl alcohol and sodium deoxycholate were studied for their use as stabilizing agents at varying concentrations. The formulations were studied for their particle size, zeta potential, entrapment efficiency and solid state characteristics, and also were tested for their in vitro cytotoxicity and in vivo behavior in rats.
Key findings: The entrapment ranged from 35 to 85%, depending on the drug-polymer ratio used. Particle size ranged from 100 to 350nm with optimal zeta potential. Accordingly, discrete spherical nanoparticles with smooth surface were obtained as evidence from Field Emission Scanning Electron Microscopy (FESEM) study. The solid state characteristics revealed dispersion of drug at the molecular level in the polymeric matrix of nanoparticles. A non-Fickian transport with initial burst release followed by slow release was observed with nanoparticles. The remarkable decrease in cell viability at various time points was observed for PLGA nanoparticles compared to other polymer matrices. The AUC(0→∞) of PLGA, PLA and PCL nanoparticles were found to be 4.77, 19.31 and 19.81 fold higher than (p<0.05) anastrozole in solution, respectively. Also, pharmacokinetics study revealed the long time circulation of anastrozole loaded polymeric nanoparticles.
Significance: The results suggest that developed nanoparticles could be used successfully for effective management of breast cancer chemotherapy.
Keywords: Anastrozole; Cytotoxicity; PCL; PLA; PLGA; Pharmacokinetic study.
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