Fabrication of lomustine loaded chitosan nanoparticles by spray drying and in vitro cytostatic activity on human lung cancer cell line L132

Abstract

This study was aimed to develop lomustine loaded chitosan nanoparticles using a homogenization and spray drying technique. Effect of crosslinking agents (sodium tripolyphosphate (TPP), and sodium hexametaphosphate (HMP)) were studied on the leaching of drug, water uptake of hydrogels, drug release from matrix and its mechanism. Nanoparticles were obtained in the average size range of 111±16.2 to 942±11.7 nm with polydispersity index (PDI) from 0.116±0.039 to 0.517±0.037. Zeta potential of nanoparticles was ranged from 29.0±1.1 to 56.0±1.1 mV. The % encapsulation efficiency of nanoparticles ranged between 58±0.88% and 96±0.51%.nanoparticles were coated with PEG 6000 to modulate drug release. Swelling index of chitosan-TPP and chitosan-TPP-PEG nanoparticles was about 428% and 350% over the 4 h and it was more (about 465% and 395%) for chitosan-HMP and chitosan-HMP-PEG nanoparticles. Drug release was sustained and diffusion controlled. Optimized formulation was tested for anticancer activity and drug retention study. Cytotoxicity on human lung cancer cell line L132 was studied by trypan blue dye exclusion test. Drug loaded nanoparticles killed L132 cells more efficiently than the corresponding drug alone (p< 0.05). Due to the increased surface area lomustine loaded TPP and HMP crosslinked chitosan nanoparticles showed better anticancer activity.