Roll No.: NIPER0911PC14
AIM: Pegylated Solid lipid nanoparticles (pSLN) mediated targeted delivery of Vinblastine and Zosiquidar to overcome Tumour drug resistance.
Development of drug resistance is a major obstacle to the success of cancer chemotherapy. Overexpression of drug efflux transporters in tumour cells results in the development of drug resistance. Of these mechanisms, overexpression of P-glycoprotein (P-gp), a drug efflux transporter, is the most commonly encountered. PEG functionalized Solid lipid nanoparticles (pSLN) encapsulating Vinblastine and Zosiquidar can be used to overcome tumour drug resistance.
1) PEG functionalized Solid lipid nanoparticles (pSLN) can be prepared by a) Cold homogenization technique.
b) Emulsion Evaporation Solidification method
2) Characterization of pSLN can be done using
a) Particle size analysis by Photon correlation Microscopy; b) Zeta-potential determination by Zeta sizer;
c) Entrapment efficiency can be calculated by Ultracentrifugation or HPLC; d) Surface analysis can be done by Transmission Electron Microscopy (TEM).
3) Cell culture study can be done to determine Vinblastine cellular uptake and accumulation in drug resistance cell.
Inclusion of Zosiquidar along with Vinblastine in PEG functionalized Solid lipid nanoparticles (pSLN) may be resulted in significantly enhanced cellular accumulation of Vinblastine and greater cytotoxicity in drug-resistant tumour cells.
1) Manthena V.S. Varma, Yasvanth Ashokraj, Dey S. Chinmoy, Panchagnula Ramesh., 2003. P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement, Pharmacological Research, 48, 347–359.
2) Breier Albert, Miroslav Barancík, Zdenka Sulová., 2005. P-Glycoprotein Implications of Metabolism of Neoplastic Cells and Cancer Therapy....