Controlled release studies of antimalarial 1, 3, 5-trisubstituted-2-pyrazolines from biocompatible chitosan-heparin Layer-by-Layer (LbL) self assembled thin films

Abstract

Herein we report the in-vitro controlled release properties of 1, 3, 5-trisubstituted-2-pyrazolines through Layer-by-Layer (LbL) self assembled thin films fabricated from chitosan and heparin sodium salt as biocompatible polyelectrolytes. This study was carried out as a preliminary step towards the applicability of LbL technique in prophylactic drug delivery of antimalarial drugs. The growth of LbL self assembly was monitored by UV-Visible spectrophotometry and Quartz Crystal Microbalance (QCM). The loading as well as in-vitro release studies (in phosphate buffer saline at pH 7.4) were carried out using UV-Visible spectroscopy. Three compounds having good antimalarial activity were tested and the release rate was found inversely proportional to the hydrophobicity of the drug. Pzln-4 has shown best release among all the three compounds (up to 780 min) followed by Pzln-5 and Pzln-8. The release trend was that of a fast release up to first 2 h followed by a steady release. Kinetic fitting of the data confirmed the process of drug release followed a pseudo second order kinetics (R(2)≥0.99). A large value of rate constant (k) revealed a faster release. Pzln-4 has shown smallest value of k corresponding to slowest release among all the three compounds.

Keywords: Antimalarials; Biocompatible; Controlled release; Polyelectrolytes; Quartz crystal microbalance.