Rational design of polysorbate 80 stabilized human serum albumin nanoparticles tailored for high drug loading and entrapment of Irinotecan

Abstract

Human serum albumin (HSA) nanoparticles are considered to be versatile carrier of anticancer agents in efficiently delivering the drug to the tumor site without causing any toxicity. The aim of the study was to develop stable HSA nanoparticles (NPs) of drug irinotecan (Iro) having slightly water solubility and moderate HSA binding. A novel strategy of employing a hydrophilic non-ionic surfactant polysorbate 80 which forms protein-polysorbate 80 complex with increased affinity and improvement in Iro-HSA binding has been used to maximize the loading and entrapment efficiency of Iro in HSA-NPs. Bespoke nanoparticles with entrapment efficiency (79.09%) and drug loading of 9.62% could be achieved with spherical shape and particle size of 77.38 nm, 0.290 polydispersity index and -23.7 mv zeta potential. The drug entrapment in nanoparticles was confirmed by Differential Scanning Calorimeter, Fourier Transformation Infrared Spectroscopy and Fluorescence spectroscopy. In-vitro release of Iro from nanoparticles showed biphasic-release with initial burst followed by prolonged release upto 24h.The short-term stability investigation of nanodispersion showed no significant changes in physicochemical properties of nanoparticles. Long-term studies on freezedried Iro-HSA-NPs indicated good stability of nanoparticles up to 12 months. This is the first report for efficient fabrication of Iro delivery system based on HSA nanoparticles. [Abstract copyright: Copyright © 2017. Published by Elsevier B.V.]