Preparation and In-vitro Evaluation of Levan Micelles: A Polyfructan Based Nano-carrier for Breast Cancer Targeted Delivery

Abstract

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 is overexpressed in the breast cancer cells. 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 0.125µM corresponding to 0.1mg/mL using pyrene I3/I1 method. At critical micelle concentration (CMC), levan formed very mono-disperse (PDI-0.082) micellar particles with a particle size of 153.1 ± 2.31nm and -14.6 ± 2mV 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 in breast cancer cell line. The IC50 value obtained was 1.525 ± 0.11nM 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 to parenteral administration. This solution containing drug was found to be hemocompatible when added to bovine blood in 1:4 ration. Micelles are proven fairly compatible on the basis of hemolysis test results.