Metformin-loaded chitosomes for treatment of malignant pleural mesothelioma - A rare thoracic cancer.

The purpose of this study was to design and evaluate chitosan dispersed lipid vesicles (chitosomes) as potential delivery carriers for repurposing metformin (Met) against malignant pleural mesothelioma. Chitosomes were prepared by directly hydrating the thin lipid film using chitosan solution as hydration medium, instead of using it as a coating agent. Developed chitosomes demonstrated spherical morphology, positive surface charge (~30 mV) and ~60% encapsulation efficiency. The calorimetric studies and X-ray diffraction pattern of Met-loaded chitosomes confirmed the successful encapsulation of Met inside the chitosome vesicles. Optimized chitosome formulation showed ~70% drug release in 72 h, displaying prolonged and controlled release of drug. Results demonstrated that Met encapsulated chitosomes possessed enhanced cellular internalization and improved cytotoxic potential. Our findings also supported inhibitory activity of chitosomes against metastatic property of pleural mesothelioma cells. The in-vitro tumor simulation studies further established anti-tumor activity of Met encapsulated chitosomes as supported by reduction in tumor volume and presence of minimal viable cells in tumor mass. The obtained results establish the effectiveness of chitosomes as delivery carrier for Met as treatment alternative for malignant pleural mesothelioma.