Preparation and evaluation of warfarin-β-cyclodextrin loaded chitosan nanoparticles for transdermal delivery

The main objective of the present work was to prepare warfarin-beta-cyclodextrin (WAF-beta-CD) loaded chitosan (CS) nanoparticles for transdermal delivery. CS is a hydrophilic carrier therefore, to overcome the hydrophobic nature of WAF and allow its incorporation into CS nanoparticles, WAF was first complexed with beta-cyclodextrin (beta-CD). CS nanoparticles were prepared by ionotropic pre-gelation using tripolyphosphate (TPP). Morphology, size and structure characterization of nanoparticles were carried out using SEM, TEM and FTIR, respectively. Nanoparticles prepared with 3:1 CS:TPP weight ratio and 2 mg/ml final CS concentration were found optimum. They possessed spherical particles (35 +/- 12 nm diameter) with narrow size distribution (PDI = 0.364) and 94% entrapment efficiency. The in vitro release as well as the ex vivo permeation profiles of WAF-beta-CD from the selected nanoparticle formulation were studied at different time intervals up to 8 h. In vitro release of WAF-beta-CD from CS nanoparticles followed a Higuchi release profile whereas its ex vivo permeation (at pH 7.4) followed a zero order permeation profile. Results suggested that the developed WAF-beta-CD loaded CS carrier could offer a controlled and constant delivery of WAF transdermally. (C) 2012 Elsevier Ltd. All rights reserved.