Abstract
Background: Liposomes serve as delivery systems for biologically active compounds. Existing technologies inefficiently encapsulate large hydrophilic macromolecules, such as PVP-conjugated chlorin e6 (Photolon). This photoactive drug has been widely tested for therapeutic applications, including photodynamic reduction of atherosclerotic plaque. Methods: A novel formulation of Photolon was produced using “gel hydration technology”. Its pharmacokinetics was tested in Sus scrofa f. domestica. Its cellular uptake, cytotoxicity, and ability to induce a phototoxic reaction were demonstrated in J774A.1, RAW264.7 macrophages, and vascular smooth muscle (T/G HA-VSMC) as well as in vascular endothelial (HUVEC) cells. Results: Developed liposomes had an average diameter of 124.7 ± 0.6 nm (polydispersity index (PDI) = 0.055) and contained >80% of Photolon). The half-life of formulation in S. scrofa was 20 min with area under the curve (AUC) equal to 14.7. The formulation was noncytotoxic in vitro and was rapidly (10 min) and efficiently accumulated by macrophages, but not T/G HA-VSMC or HUVEC. The accumulated quantity of photosensitizer was sufficient for induction of phototoxicity in J774A.1, but not in T/G HA-VSMC. Conclusions: Due to the excellent physical and pharmacokinetic properties and selectivity for macrophages, the novel liposomal formulation of Photolon is a promising therapeutic candidate for use in arteriosclerosis treatment when targeting macrophages but not accompanying vascular tissue is critical for effective and safe therapy.
Highlights
Liposomes in the form of lipid, large, unilamellar vesicles are promising delivery systems for biologically active compounds including biological macromolecules and polymers [1,2]
Using cell lines relevant to planned application to vascular smooth muscle, vascular endothelial, and activated macrophage cell line, we showed that the novel liposomal formulation did not exert any significant dark cytotoxicity, which is consistent with data obtained with other chlorin-related compounds [22,26,30]
We have shown that Photolon liposomal formulation is preferentially accumulated in macrophages, but not in the smooth muscle or endothelial cell lines
Summary
Liposomes in the form of lipid, large, unilamellar vesicles are promising delivery systems for biologically active compounds including biological macromolecules and polymers [1,2]. The existing technologies of liposome production, such as “dry lipid film”, reverse phase evaporation, “ethanol injection”, and “proliposome” creation using fluid bed coating or high pressure homogenization allow for the encapsulation of a hydrophilic active compound, but the resulting liposomes typically exhibit limited encapsulation efficiency [10,11,12]. This is mainly due to the large size of the encapsulated compound. Existing technologies inefficiently encapsulate large hydrophilic macromolecules, such as PVP-conjugated chlorin e6 (Photolon) This photoactive drug has been widely tested for therapeutic applications, including photodynamic reduction of atherosclerotic plaque. Conclusions: Due to the excellent physical and pharmacokinetic properties and selectivity for macrophages, the novel liposomal formulation of Photolon is a promising therapeutic candidate for use in arteriosclerosis treatment when targeting macrophages but not accompanying vascular tissue is critical for effective and safe therapy
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