Controlled release of curcumin and gemcitabine from mucoadhesive chitosan-gelatin polymeric ovules: Cytotoxic effects on cervical cancer cells

Abstract

Cervical cancer (CxCa) is the fourth most common type of neoplasm affecting the global female population. Treatment for CxCa typically involves the systemic administration of chemotherapeutic agents. However, these treatments often result in fatigue, increased risk of infection, nausea, vomiting, hair loss, loss of appetite, and diarrhea. Therefore, it is crucial to explore new drugs and site-specific drug delivery strategies to combat cervical neoplasia. This study aimed to design vaginal suppositories based on chitosan–gelatin that enable mucoadhesion and the release of curcumin and gemcitabine and to evaluate their effects on HeLa cells. Gelatin-chitosan ovules loaded with curcumin and gemcitabine were successfully formulated. The uptake of simulated vaginal fluid (SVF) resulted in an increase in weight ranging from 40 % to 80 %. The ovules exhibited porosity and hydrophilicity and demonstrated mucoadhesive properties on porcine vaginal tissue. After 8 h of incubation at 37 °C, ovules containing 10 % gelatin released more curcumin, while those with 10 % and 20 % released more gemcitabine. Curcumin and gemcitabine exhibited cytotoxic effects on HeLa cells, with IC₅₀ values of 13.47 µM and 0.15 µM, respectively. Furthermore, it was observed that curcumin reversed gemcitabine-induced necrosis and promoted a mechanism like apoptosis or necroptosis. These findings suggest that ovules loaded with curcumin and gemcitabine can potentially serve as a site-specific treatment for CxCa.