Stable Dipalmitoylphosphatidylcholine Liposomes Coated with an F127 Copolymer for Hypericin Loading and Delivery

Over the past decade, hypericin (Hy) has been used by several researchers due to its broad therapeutic potential against microorganisms and cancer cells. Considering the high hydrophobicity of Hy, its application in the biological medium becomes limited. In recent works, our research group has shown the potential of the liposomes to solubilize and carry Hy with high efficiency in different photodynamic therapy (PDT) applications. Moreover, previous works have shown that copolymer-coated liposomes have emerged as a smart alternative to conventional liposomes due to their targeting kinetic stability and prolonged circulation time in blood. About this approach, we report here a Hy delivery system based on the use of copolymer-lipid liposomal vesicles. We achieve a better proportion between the F127 copolymer and 1,2-dipalmitoyl-sn-3-glycerol-phosphatidylcholine by applying kinetic studies of association. The findings show that Hy was incorporated into the self-assembled copolymer-lipid with a t1/2 value five times lower, when compared to the conventional vesicles. The copolymer-lipid was subjected to cycles of thermal and temporal variations as well as to freeze-drying and reconstitution processes. We show that the F127 acts as a protective agent, keeping the copolymer-lipid/Hy stable for 6 months in the solid state, without the use of a cryoprotectant. The coated vesicles loading Hy showed high stability in the aqueous medium by 20 days, even when the temperature changed. Location studies by the fluorescence technique revealed specific interaction binding sites between the copolymer-lipid-coated and Hy molecules, showing that F127 plays an important role in the higher Hy solubilization. According to our results, we believe that this coated system is a potential Hy delivery system to PDT medical applications.