Preparation and in vitro–in vivo evaluation of surface-modified poly(lactide-co-glycolide) nanoparticles as controlled release carriers for flutamide delivery

Abstract

This investigation explores the use of methoxy polyethylene glycol (mPEG) functionalised poly(d,l-lactide-co-glycolide) (PLGA) nanocrystals of flutamide (FLT) with enhanced solubility, bioavailability and blood circulation time for targeting prostate cancer. FLT had Log P 3.27, short half life 5–6 h, low water solubility, permeability and bioavailability with extensive first-pass metabolism. FLT-loaded nanocrystals were prepared using nanoprecipitation method with surface coating by mPEG and characterised through differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray powder diffraction, scanning electronic microscopy, particle size, zeta potential, percent entrapment efficiency (% EE), in vitro dissolution, haemolysis, sterility, bioavailability and stability studies. The percent cumulative drug release and % EE of optimised formulation was found to be 95.21 ± 1.18 and 88.36 ± 1.20, respectively, for 48 h. In addition, FLT-loaded PEGylated PLGA nanocrystals exhibited significantly delayed blood clearance with drug level of about 766.71 ng/mL at 48 h. In conclusion, PEGylated PLGA FLT nanocrystals could be demonstrated as a novel approach to enhance solubility, bioavailability and blood circulation time.

• Injectables
• nanoparticle
• pharmacokinetics
• PLGA
• zeta potential

Acknowledgements

The authors are grateful to Cipla (I) Ltd, Bangalore, India, and Wockhardt Ltd., Aurangabad, India, for the gift sample of Flutamide and PLGA. The authors would like to thank Dr. S. J. Surana, Principal (R C Patel Institute of Pharmaceutical Education & Research, Shripur, Maharashtra, India) for providing the facilities necessary to carry out our research work.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.