Formulation and Characterization of Phospholipid Based Micelles: A Potential Carrier for Cancer

Mayank Chaudhari, Deepa H. Patel*, Drashti G. Pathak, Sneha K. Patel,
Associate Professor, Parul Institute of Pharmacy and Research, P.O. Limda, Ta. Waghodia, Dist. Vadodara-391760

A B S T R A C T
Cancer is a broad group of diseases involving unregulated cell growth. In cancer, cells divide and grow uncontrollably; forming malignant tumors. Mitoxantroneis an anthracenedione antineoplastic agent. It is a potent inhibitor of topoisomerase II that intercalates into deoxy-ribonucleic acid (DNA) through hydrogen bonding, causes cross links and strand breaks. However, it has a cytocidal effect on both proliferating and non proliferating cultured human cells, suggesting lack of cell cycle phase specificity, which prompt for development of novel carrier that could effectively target tumor site without producing undesirable side effects. The aim of the present investigation was to formulate and evaluate phospholipids based micelles: A potential carrier for anticancer drug, mitoxantrone. Fourier transform infrared spectroscopy (FTIR) was employed to study drug-excipient incompatibility. Analytical method was performed by UV spectrophometer. Phospholipids Micelles were prepared by co-precipitation and reconstitution of drug and phospholipids. Phospholipids micelles were successfully prepared by taking the ratio of Mitoxantrone:Phospoipids (1:3) and N-(carbonyl-methoxy polyethylene glycol-2000)- 1,2-distearoyl-sn-glycero-3 phosphoethanolamin (DSPE MPEG 2000) : Phosphatidylcholine (PC) (7:3) by co-precipitation method and evaluated for micelles size and zeta potential, percent drug entrapment, micelles morphology using transmission electron microscopy (TEM), in vitro drug release, sterility testing and stability studies.  Drug and excipients were found to be compatible to each other which were confirmed by FTIR study.The micelles size, zeta potential and percent entrapment was found to be 23.3±3.12 nm, -40.6±0.21mV and 91±0.06 respectively. In-vitro drug release study of the optimized batch was found to be 97.73 ± 0.89 % for optimized batch up to 24 hrs. Sterility test suggested that the developed phospholipid micelles were successfully sterile using membrane filtration method. Stability study shows phospholipids micelles were stable at refrigerated condition. The present study demonstrated that, phospholipids micelles are a promising nanocarrier for mitoxantrone delivery to cancer cell and should be used as a novel targeted nanomedicine.
Keywords: Mitoxantrone, N-(carbonyl-methoxy polyethylene glycol-2000)- 1,2-distearoyl-sn-glycero-3phosphoethanolamin (DSPE MPEG 2000), Phosphatidylcholine (PC) , Phospholipids Micelles.