Design, Development and Optimization of Topotecan Hydrochloride Solid Lipid Nanoparticles for Oral Chemotherapy

The objective of this research work was to formulate and evaluate solid lipid nanoparticles of anticancer drug topotecan hydrochloride in order to sustain its release and therefore improve its therapeutic outcomes. SLNs were prepared by hot micro emulsion method using glyceryl monostearate as lipid carrier and Tween 80 as surfactant in specific proportions. FT-IR and DSC studies revealed that there was no interaction between drug and lipid. The effect of drug: lipid ratio, surfactant concentration, speed and time of homogenizer on drug release, particle size and EE were studied. The results of particle size, encapsulation efficiency and in vitro drug release at 12hr fell between 111.9 nm and 255nm, 65.12% and 77.63%, and 72.31 and 79.79% respectively. Optimized formulation showed release of drug up to 73.47 % at 12 hrs, entrapment efficiency of 77.75 % and particle size of 158.0 nm. The analysis of 3-D graphs revealed that parameters such as drug: lipid ratio and time of homogenization have a profound effect on both encapsulation efficiency and cumulative drug release. Scanning electron microscopy studies showed particles with disuniform surface and shape. The drug release from optimized formulation was found to fit best into first order kinetic model. It also showed almost linear regression in Higuchi’s plot suggesting that diffusion is one of the mechanisms for drug release and n value of Korsmeyer-Peppas plot was found to be 0.716 indicating that the drug release did not follow fickian diffusion controlled mechanism.