Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

Site specificity of anti-neoplastics still poses a challenge in the pharmaceutical research. Conventional chemotherapy has limitations such as site non-specificity, inability of the drug to penetrate inside the tumor, adverse effects there by reducing the clinical application. So, in this study oxaliplatin solid lipid nanoparticles (OP-SLN) were prepared by micro-emulsion method using various ratios of lipid and then covalently conjugated to TRAIL monoclonal antibody (TR-OP-SLN) for targeting colorectal cancer cells by receptor mediated internalization of drug. The prepared immuno nanoparticles were characterized for Fourier Transform Infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), particle size, scanning electron microscopy (SEM), surface charge, fluorescence intensity and in vitro drug release. These were further characterized for in vitro cytotoxicity (in HT-29 cells) followed by cellular uptake and internalization by Flow Cytometry along with protein assay. The optimized OP-SLN3 has shown an appreciable particle size (121�?±1.22 nm), entrapment efficiency (78�?±0.09%), and drug loading (32�?±1.01%) along with spherical surface morphology. TR-OP-SLN has shown a drug release of 81�?±0.01% and 27�?±0.12% at pH 4.5 and 7.4 respectively further confirming its ability to release the drug inside the tumor. Fluorescence study confirmed the presence of the antibody on the surface of the nanoparticles by change in their intensity. A 1.5 fold increase in cytotoxicity of immuno nanoparticles (7.5 �?¼g/ml or more) was observed. Cellular uptake studies have shown 89% of immuno nanoparticles uptake by the cells and immuno nanoparticle are majorly internalized in the perinuclear region. In conclusion, we demonstrate a preparation and characterization of oxaliplatin immuno nanoparticles for receptor mediated targeting of the drug.

Biography

Email: tummala.shashank@outlook.com