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.

Novel resveratrol and 5-fluorouracil coencapsulated in PEGylated nanoliposomes improve chemotherapeutic efficacy of combination against head and neck squamous cell carcinoma.

Increasing consumption of tobacco and alcohol has led to a steady increase in the incidence of head and neck cancers in Asia. The drawbacks associated with the existing chemotherapeutic and surgical interventions have necessitated the development of a safer alternative for therapy of head and neck cancers. In this study we have explored the synergistic therapeutic potential of a phytochemical and chemotherapeutic agent using PEGylated liposomes as a delivery vehicle. Resveratrol and 5-fluorouracil were successfully coencapsulated in a single PEGylated nanoliposome. The thermal analysis and the nuclear magnetic resonance results revealed that resveratrol localized near the glycerol backbone of the liposomal membrane while 5-fluorouracil localized closer to the phosphate moiety, which influenced the release kinetics of both drugs. The nanoformulation was tested in vitro on a head and neck cancer cell line NT8e and was found to exhibit a GI50 similar to that of free 5-fluorouracil. Further, gene expression studies showed that the combination of resveratrol and 5-fluorouracil exhibited different effects on different genes that may influence the net antagonistic effect. The coencapsulation of resveratrol and 5-fluorouracil in a liposomal nanocarrier improved the cytotoxicity in comparison with the free drug combination when tested in vitro.

Combinations of plant polyphenols & anti-cancer molecules: a novel treatment strategy for cancer chemotherapy.

The investigation of chemotherapeutic agents for the treatment of cancer since the early 1940s has resulted in the discovery of over 50 drugs till date. However, most of these drugs result in severe side effects causing physical and mental trauma to patients. In order to eliminate the side effects, search for better and safer drugs has been ongoing for several decades, which has resulted in the discovery of anti-cancer properties of many phytochemicals. Polyphenols represent a unique class of phytochemicals that possess excellent anti- oxidant, anti-inflammatory properties and also modulate cell signalling pathways leading to anti-cancer effects. However, the use of these compounds as anti-cancer agents is not as effective and hence combinations of chemotherapeutic drugs with these molecules have been attempted. Promising results in in vitro and in vivo experiments while using combinations of polyphenols and chemotherapeutic agents open up new avenues for the discovery of the ideal drug combinations for cancer therapy. This review highlights the efficacy of the combination of phytochemicals with synthetic anti � neoplastic drugs over the conventional combinations of anti-neoplastic drugs and the possible interventions in the clinical settings. The review also discusses the inclusion of polyphenols in emerging therapeutic modalities like nanotechnology and photodynamic therapy.

Dose-dependent interaction of trans-resveratrol with biomembranes: effects on antioxidant property.

The present study investigates dose-dependent effects of trans-resveratrol on the membrane fluidity using planar lipid bilayer and liposome models. The complex admittance plots obtained for the lipid bilayer show that resveratrol below 60 µM preferentially interacts with the polar headgroups at the membrane-electrolyte interface, leading to enhanced membrane admittance and vice versa at higher concentrations (>60 µM). This was confirmed using solid-state (13)C and (31)P NMR studies and membrane fluidization studies. The localization of resveratrol in the membrane bilayer was found to alter the membrane rigidity, which resulted in a dose-dependent blebbing and lysis of erythrocytes. The protective effect of trans-resveratrol against DPPH also confirms that its localization in the hydrophobic region prevents lipid peroxidation. The cytotoxic effect of resveratrol on a breast cancer cell line also displays a progressive pattern, indicating possible correlation with its membrane rigidifying properties and localization in the lipid bilayer.