Encapsulation of orlistat in biodegradable polymeric nanocapsules improves its cytotoxic effect against cervical cancer cells

Orlistat (ORL) is an FDA-approved drug to treat obesity that has demonstrated promising anticancer properties due to inhibition of fatty acid synthase (FASN). FASN overexpression has been reported in different cancer cell lines, including cervical cancer cells, as recently reported by our group. However, ORL has poor water solubility and low oral bioavailability, limiting its formulation and clinical use. Therefore, new strategies must be considered to improve its intrinsic solubility and consequently, enhancing its therapeutic properties. So, in this study we evaluate the effects of the ORL encapsulation in polymeric aqueous nanocapsules (NC) on its in vitro cytotoxic activity in a cervical cancer cell line (HeLa). NC containing ORL (NC-ORL) were prepared using poly (epsilon-caprolactone) by the interfacial deposition of preformed polymer method. Cell counting by flow cytometry was used to evaluate the in vitro antiproliferative effect of encapsulated ORL in HeLa cells after 48 h of treatment. The nanoformulations had a mean z-average between 210 and 220 nm and an ORL encapsulation efficiency of almost 100 %. Placebo NC were not toxic to HeLa cells under the experimental conditions, whereas the nanoencapsulation of ORL improved the cytotoxic effect compared to non-encapsulated ORL. Therefore, this novel nanoformulation can be suggested as a promising alternative for the treatment of cervical cancer, overcoming the low ORL intrinsic solubility and opening the doors for the development of delivery systems for local administration to fight against the cervical cancer, a globally women's health concern.