Dual drug loaded nanoliposomal chemotherapy: A promising strategy for treatment of head and neck squamous cell carcinoma

The rising incidence of head and neck cancer and the drawbacks of currently used therapeutic strategies such as salvage surgery followed by adjuvant chemo- or radiotherapy have encouraged pursuits for better therapeutic approaches. This work describes the development and characterization of a PEGylated liposomal nanocarrier encapsulated with trans-resveratrol (Res), a plant stilbenoid, and doxorubicin hydrochloride (Dox), a standard chemotherapeutic agent for treatment of oral squamous cell carcinoma. The two drugs were loaded in liposomes prepared from egg phosphatidylcholine and DSPE-PEG with maximum encapsulation efficiencies of about 80% for each drug achieved at Res to Dox ratio of 2:1. The liposomal suspension was found to be stable with a zeta potential of −30.53 mV and size of approximately 250 nm. Thermal properties and release kinetics of the dual drug loaded liposomes were determined. The nanoformulation was evaluated for its in vitro anticancer efficacy on an oral squamous cell carcinoma cell line (NT8e). The cell uptake mechanism of the liposomal formulation was determined using pharmacological inhibitors for different endocytosis pathways. The combination effect of the two drugs was evaluated in free form and was found to have synergistic effects. The formulation was found to have a higher IC50 value than that of free doxorubicin hydrochloride but was found to have a superior effect on the signaling proteins involved in apoptosis and cell cycle.

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