Development, evaluation and biodistribution of stealth liposomes of 5-fluorouracil for effective treatment of breast cancer

Abstract

The current research was undertaken to design stealth liposomes of 5-Fluorouracil for reducing its cardiotoxicity and prolong the half-life by developing long-circulating liposomes. The liposomes were prepared by the NH₄EDTA gradient method, where EDTA is used as a cardioprotectant. Ascorbyl-6-palmitate was also used which helped for the synergistic effect of 5-Fluorouracil to counteract the cancer cells and provide promising application in the treatment of breast cancer cells. Taguchi design was used for screening of formulation and HSPC phospholipid was selected. The drug-excipient compatibility was checked through FTIR which showed all the excipients were compatible with the drug. The formulation was optimized by using 3² factorial design. The drug to lipid ratio (1:5) and Ascorbyl-6-Palmitate concentration (15 mg) were selected. The vesicle size of the prepared liposomes was found to be 70.12 ± 0.58 nm and uniform distribution was observed. The zeta potential and entrapment efficiency of the stealth liposomes were found −16.28 mV and 92 ± 0.007% respectively. In-vitro drug release study of formulation showed drug release of 63.50 ± 0.94% in 24 hrs. The formulation was sterilized by 0.22 µm Mixed cellulose esters (MCE) membrane filter and passed sterility test. Moreover, a biodistribution study was performed by Fluorescence microscopy and by HPLC method, which showed formulation was circulated for 24 hours. Finally, a cell line study indicated that prepared formulation possess greater anti-tumour activity. The cardiotoxicity study revealed that the stealth liposomes have minimum cardiotoxicity as compare to the plain drug.

Keywords:

• 5-Fluorouracil
• EDTA
• ascorbyl-6-palmitate
• breast cancer
• MCF-7

Disclosure statement

No potential conflict of interest was reported by the author(s).