Effects of triglycerides on the hydrophobic drug loading capacity of saturated phosphatidylcholine-based liposomes

A high drug-loading capacity is a critical factor for the clinical development of liposomal formulations. The accommodation of hydrophobic drugs within the liposomal membrane is often limited in saturated phosphatidylcholine (PC)-based liposomes owing to the rigidity of the lipid acyl chain. In the current study, we explored the possibility of improving the hydrophobic drug loading capacity of liposomes by incorporating triglyceride into liposomal membranes. Incorporation of Captex 300, a medium chain triglyceride, into liposomes composed of dimyristoylphosphatidylcholine and cholesterol greatly increased the fluidity and lamellarity of the resultant liposomes. Liposomal incorporation of medium or long chain, but not short chain, triglycerides greatly enhanced the concentration of loaded paclitaxel (PTX) in saturated PC-based liposomes. The enhancing effect of triglyceride saturated at a triglyceride content corresponding to the amount required to fluidize the liposome structure. In addition, the enhancing effect was not observed in unsaturated PC-based liposomes and was not associated with the solubility of PTX in each triglyceride. Triglycerides also enhanced the loading of docetaxel, another hydrophobic drug. Taken together, our results suggest that triglyceride incorporation in saturated PC-based liposomes provide an improved dosage form that enables increased hydrophobic drug loading by altering the fluidity and structure of liposomal membranes.

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