title: 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.
authors.affiliation: Department of Pharmaceutics and Quality Assurance, R C Patel Institute of Pharmaceutical Education and Research , Shirpur, Dhule, Maharashtra , India.
authors.forename: Pradum Pundlikrao
authors.initials: PP
authors.lastname: Ige
authors.forename: Solanki Nirmal
authors.initials: SN
authors.lastname: Dipsingh
mesh_terms: D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems; D005485:Flutamide / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D017207:Rats, Sprague-Dawley
chemical_list: D000726:Androgen Antagonists; D003692:Delayed-Action Preparations; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D005485:Flutamide
keywords: Injectables; PLGA; nanoparticle; pharmacokinetics; zeta potential