Development of Block Co Polymeric Micelles of Erlotinib as Targeted Therapeutics for Lung Cancer

Abstract

Erlotinib is epidermal growth factor receptor inhibitors used as anticancer first line therapy to treat non-small cell lung cancer. However, its low water solubility, along adverse drug reactions from deposition in normal cells, limits its use in therapy. Erlotinib self assembles mixed mixed micelles were developed and optimized. Self-assembled mixed micelles were characterized for micellar size, PDI, entrapment efficiency. Invotro drug release reveled initially brust release and more fluctuations in plasma drug concertration. To overcome such limitation surface conjugated block co polymeric micelles were developed. Biotin conjugated pluronic F68-Polycaprolectone have been used to improve pharmacokinetics of drug and reduce its toxicity/ In this study Block co-polymer (Biotin-F68-PCL) were synthesized and cgaracterized for the structural conformation by FTIRand NMR spectroscopy. Quality by design, a statical tool was applied for optimization of various parameters that impact micelle size, entrapment efficiency and zeta potential. Design matrix generated using minitab software and graphical presentation via contour plot revealed science-based development of formulation and resulted in requisite micellar size of 115.1 nm and entrapment efficiency of 94%± 1:5. Drug release of optimized block co-polymeric micelles was found to be slow and controlled release and is approximately pH dependent. The MTT cell assay and cellular uptake on A549 cell line shows better cell inhibition of Biotin-F68-PCL compared to F68-PCl and erlotinib drug. In nutshell, Biotinylated block copolymeric mecelles would be platform delivery for targeting anticancer agent to treat non small cell lung cancer. newline