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Cyclic dipeptides have been well characterized for their biological activity, including antimicrobial and anticancer activities. Cyclo(His-Gly) and cyclo(His-Ala) have also recently demonstrated significant anticancer activity against a range of cell lines, however, as a result of their physicochemistry, namely high solubility and low lipophilicity, it can be predicted that cellular permeability would be low, making them ideal candidates for liposome drug delivery. Liposomes were composed of phosphatidylcholine, hydrogenated soy phosphatidylcholine (HSPC), stearylamine, -tocopherol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (PEG-DSPE) or folate-polyethylene glycol-cholesteryl hemisuccinate (F-PEG-CHEMS) using the thin-film hydration method and characterized for size and encapsulation. The cytotoxic activity of the encapsulated cyclic dipeptides was tested against HeLa, low folate HeLa and MCF-7 cells and found to have limited improvement in activity. However, modification of the polyethylene glycol with folic acid to target folate receptors significantly decreased the IC50 values recorded in all cells lines tested, particularly HeLa cells cultured in media containing physiological concentrations of folic acid with the lowest IC50 being recorded as 0.0962mM for folate-targeted cyclo(His-Ala). Therefore, hydrophilic cyclic dipeptides are ideal candidates for inclusion into targeted drug delivery systems such as liposomes.

Cyclic dipeptides have been well characterized for their biological activity, including antimicrobial and anticancer activities. Cyclo(His-Gly) and cyclo(His-Ala) have also recently demonstrated significant anticancer activity against a range of cell lines, however, as a result of their physicochemistry, namely high solubility and low lipophilicity, it can be predicted that cellular permeability would be low, making them ideal candidates for liposome drug delivery. Liposomes were composed of phosphatidylcholine, hydrogenated soy phosphatidylcholine (HSPC), stearylamine, -tocopherol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (PEG-DSPE) or folate-polyethylene glycol-cholesteryl hemisuccinate (F-PEG-CHEMS) using the thin-film hydration method and characterized for size and encapsulation. The cytotoxic activity of the encapsulated cyclic dipeptides was tested against HeLa, low folate HeLa and MCF-7 cells and found to have limited improvement in activity. However, modification of the polyethylene glycol with folic acid to target folate receptors significantly decreased the IC50 values recorded in all cells lines tested, particularly HeLa cells cultured in media containing physiological concentrations of folic acid with the lowest IC50 being recorded as 0.0962mM for folate-targeted cyclo(His-Ala). Therefore, hydrophilic cyclic dipeptides are ideal candidates for inclusion into targeted drug delivery systems such as liposomes.