Dual delivery of metformin and Y15 from a PLGA scaffold for the treatment of platinum-resistant ovarian cancer.

Abstract

Aims: Drug-loaded poly(lactic-co-glycolic acid) (PLGA) scaffolds were fabricated using a mold-less technique to investigate whether the combined delivery of both Y15 (FAK inhibitor) and metformin would result in enhanced effects on cell viability compared to the release of each drug alone for the treatment of platinum-resistant ovarian cancer (PROC).

Materials & methods: Scaffolds were fabricated using an easy and economical mold-less technique that combined PLGA and the drugs (i.e. metformin and/or Y15) in tetraglycol and injected in PBS, to form a globular morphology.

Results: The exposure of cells to metformin and Y15 resulted in a significantly enhanced cytotoxic efficacy compared to single-drug treatment with either metformin or Y15. When the drugs were delivered using the PLGA scaffolds, the combination of the two drugs was significantly more cytotoxic compared to scaffolds containing metformin only and Y15 only.

Conclusions: The combination of metformin and Y15 can result in an increase in antitumor activity in PROC cells through apoptosis. The delivery of both drugs from the PLGA biomaterial scaffold allowed for a more enhanced combinational effect compared to the utilization of free drugs (without a scaffold) and should be further explored as a promising treatment of PROC.