Targeting of liposome-associated calcipotriol to the skin: Effect of liposomal membrane fluidity and skin barrier integrity

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Many dermal diseases like psoriasis are characterized by major changes in skin barrier function, which challenge the reproducible delivery of drugs into specific layers of diseased skin. The purpose of this study was to elucidate how liposomal bilayer fluidity and barrier integrity affected the delivery of liposome-associated calcipotriol to the skin. Calcipotriol-containing gel state and liquid state dipalmitoylphosphatidyl-choline:dilauroylphosphatidylcholine liposomes were prepared by extrusion. Using Langmuir monolayers, calcipotriol was shown to affect the packing of the lipid membrane. The penetration of radioactively labeled lipid and calcipotriol into pig skin was examined using the Franz diffusion cell model, and tape stripping was applied to impose an impaired barrier. Distorting the skin barrier resulted in an enhanced penetration of lipid from both gel and liquid state liposomes. In addition, increased penetration of lipid from liquid state liposomes was observed compared to gel state liposomes into barrier-impaired skin. For barrier-impaired skin, an elevated calcipotriol-to-lipid ratio was found in the receptor fluid for both liposome compositions indicating that calcipotriol is released from the vesicles. This suggests that the liposome-mediated delivery of calcipotriol to the epidermis of diseased skin is affected by the fluidity of the liposomal membrane.

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