CD 253 TARGETED OXALIPLATIN LOADED IMMUNO NANOPARTICLES FOR THE TREATMENT OF COLORECTAL CANCER

Abstract

quotThe aim of this study is to prepare nanoparticles encapsulating oxaliplatin and later conjuagting them to TRAIL antibody covalently for improved site specificity along with apoptotic acitvity for colorectal tumors. newlineOxaliplatin was encapsualted into solid lipid nanoparticles and polymeric nanoparticles by microemulsion and solvent emulsification evaporation method respectively. The compatibility results demonstrated the compatibility of the excipients with the drug ensuring stability. Box-behnken design was used for the optimization of the nanoparticles. The nanoparticles optimized (OP-SLN3 and OHNPs) had shownappreciable particle size, drug loading and entrapment efficiency. In vitro drug release had shown biphasic pattern of drug release with initial burst release followedby sustained release later on. SEM and TEM studies confirmed the surface morphology of the nanoparticles. The immuno-nanoparticles were characterized for the confirmation of attachment of antibody by phycoerythrin nanoparticles visually and more homgenous distribution and intensity shift changes revealed by flow cytometry studies. In vitro cytotoxicity studies had shown enhanced apoptotic activity with IC50 values of 0.63 and#956;M for OIHNPs and 0.65 and#956;M for TR-OPSLN compared to the 3.5 and#956;M of oxalipaltin. Cellular uptake and internalization studies demonstrated the ability and specificity of the nanoparticles by their accumualtion in HT-29 cells rather than in MCF-7 cells and the co-culture studies further supported the cause. Flow cytometry studies revealed transitional S-phase delay at 72 h with G2/M cell cycle arrest. The immuno-nanoparticles were found to inhibit anti-apoptotic proteins (survivin, Bcl-2) and activate the apoptotic proteins confirmed by western blot analysis. newlineThe current drug therapy can lay a more improved foundation as an alternative to the present chemotherapy treatment by overcoming the limitations by delivering the drug to the target site specific to the protein. newlinequot newline