Experimental design of a liposomal lipid system: A potential strategy for paclitaxel-based breast cancer treatment

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2015-12, Vol.136, p.553-561
• Main Authors: Barbosa, Marcos V., Monteiro, Liziane O.F., Carneiro, Guilherme, Malagutti, Andréa R., Vilela, José M.C., Andrade, Margareth S., Oliveira, Mônica C., Carvalho-Junior, Alvaro D., Leite, Elaine A.
• Format: Article
• Language: English
• Subjects: Biotechnology; Breast; Breast Neoplasms - drug therapy; Cancer; Encapsulation; Folate; Formulations; Humans; Lipids - administration & dosage; Liposomes; Paclitaxel; Paclitaxel - therapeutic use; Patients; pH-sensitivity; Targeted drug delivery; Tumors; Viability
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2015.09.055

Long-circulating and pH-sensitive PEG-folate-coated liposomes containing PTX show high cytotoxicity against human breast cancer cell lines which over-express folate receptors. [Display omitted] •Long-circulating and pH-sensitive PEG-folate-coated (SpHL-FT-PTX) liposomes containing PTX were successfully developed and characterized.•SpHL-FT-PTX showed a good stability after storage at 4°C.•SpHL-FT-PTX showed enhanced cytotoxic activity on breast cancer cell lines. Paclitaxel (PTX) is widely used as a first-line treatment for patients with metastatic breast cancer; however, its poor water solubility represents a major challenge for parenteral administration. The encapsulation of the PTX in drug-delivery systems with high affinity for tumor sites could improve the uptake and increase its therapeutic efficacy. In this work, long-circulating and pH-sensitive PEG-coated (SpHL-PTX) and PEG-folate-coated liposomes containing PTX (SpHL-FT-PTX) were prepared, and the physicochemical properties and in vitro cytotoxic activity were evaluated. Both formulations presented adequate physicochemical properties, including a mean diameter smaller than 200nm, zeta potential values near the neutral range, and an encapsulation percentage higher than 93%. Moreover, SpHL-FT-PTX showed a good stability after storage for 100 days at 4°C. The viability studies on breast cancer cell lines (MDA-MB-231 and MCF-7) demonstrated cytotoxic activity more pronounced for SpHL-FT-PTX than for SpHL-PTX or free drug for both tumor cell lines. This activity was reduced to a rate comparable to SpHL-PTX when the cells were previously treated with folic acid in order to saturate the receptors. In contrast, in the normal cell line (L929), cell viability was decreased only by free or liposomal PTX in the highest concentrations. A significantly higher selectivity index was obtained after SpHL-FT-PTX treatment compared to SpHL-PTX and free PTX. Therefore, the results of the present work suggest that SpHL-FT-PTX can be a promising formulation for the treatment of metastatic breast cancer.