Parth Patel* and Yadvendrakumar Agrawal
Background: Levans are biopolymers of fructose, produced by different microorganisms. Fructose present in the levan micelles binds with the Glucose Transporter 5 (GLUT 5) which are over-expressed in breast cancer cell.
Objective: Increased solubility of paclitaxel by loading in the GLUT 5 transporter targeted levan based micelles may enhance its bioavailability and facilitate a targeted delivery to the breast cancer cells.
Methods and Results: Critical micelle concentration of levan with an average molecular weight of 800,000 Dalton was found to be 0.125 µM corresponding to 0.1 mg/mL using pyrene I3/I1 method. At critical micelle concentration (CMC), levan formed a very mono-disperse (PDI-0.082) micellar particles with a particle size of 153.1 ± 2.31 nm and -14.6 ± 2 mV zeta potential. In-vitro drug release study was performed to identify the fit kinetic model along with Fourier transform infrared analysis and Differential scanning calorimetry studies. In-vitro kinetic model fitting revealed first-order drug release from the prepared micellar composition. The drug loaded micellar composition was studied for its anticancer activity on breast cancer cell line. The IC50 value obtained was 1.525 ± 0.11 nM on MCF7 cell line.
Conclusion: Paclitaxel micelles showed a nineteen fold improvement in the IC50 value compared to free paclitaxel. Hemocompatibility study was performed with a view of the parenteral administration. This solution containing drug was found to be haemocopatible when added to bovine blood in 1:4 ration. Micelles are proven fairly compatible on basis of hemolysis test results.
Levan polymer, Paclitaxel, Targeted delivery, Metastatic breast cancer, IC50 value, MCF7 cell line
Institute of Research and Development, Faculty of Pharmacy, Gujarat Forensic Sciences University, Gandhinagar, Institute of Research and Development, Faculty of Pharmacy, Gujarat Forensic Sciences University, Gandhinagar