1-monooleoyl-rac-glycerol and Skin-Neoplasms

Skin dendritic cells (DCs) such as Langerhans cells and dermal dendritic cells have a pivotal role in inducing antigen-specific immunity; therefore, transcutaneous cancer vaccines are a promising strategy to prophylactically prevent the onset of a variety of diseases, including cancers. The largest obstacle to delivering antigen to these skin DC subsets is the barrier function of the stratum corneum. Although reverse micellar carriers are commonly used to enhance skin permeability to hydrophilic drugs, the transcutaneous delivery of antigen, proteins, or peptides has not been achieved to date because of the large molecular weight of drugs. To achieve effective antigen delivery to skin DCs, we developed a novel strategy using a surfactant as a skin permeation enhancer in a reverse micellar carrier. In this study, glyceryl monooleate (MO) was chosen as a skin permeation enhancer, and the MO-based reverse micellar carrier enabled the successful delivery of antigen to Langerhans cells and dermal dendritic cells. Moreover, transcutaneous vaccination with the MO-based reverse micellar carrier significantly inhibited tumor growth, indicating that it is a promising vaccine platform against tumors.

Topics: Administration, Cutaneous; Animals; Cancer Vaccines; Cell Line, Tumor; Dendritic Cells; Disease Models, Animal; Drug Carriers; Female; Glycerides; Humans; Melanoma; Melanoma-Specific Antigens; Mice; Mice, Inbred C57BL; Micelles; Skin; Skin Neoplasms; Tumor Burden; Vaccination

We designed novel polymer-free cubic bicontinuous liquid crystalline dispersions (cubosomes) using monoolein as molecular building block, phospholipids as stabilizers, propylene glycol as hydrotrope. Their kinetic stability was evaluated by analysing the backscattering profiles upon ageing, and the most stable formulation was chosen as potential photosensitizers delivery vehicle for photodynamic therapy (PDT) of human skin melanoma cells. Morphological and topological features of such formulation alternatively loaded with Chlorin e6 or meso-Tetraphenylporphine-Mn(III) chloride photosensitizing dyes were investigated by cryo-TEM, DLS, and SAXS. Bioimaging studies demonstrated that Me45 and MeWo cell lines effectively internalized these cubosomes formulations. Particularly, photodynamic activity experiments proved both the very low cytotoxicity of the cubosomes formulation loaded with Chlorin e6 dye in the "dark" condition, and its significant cytotoxic effect after photoirradiation. The toxic effect recorded when the photosensitizer was encapsulated within the cubosomes was shown to be one order of magnitude higher than that caused by the free photosensitizer. This is the first report of biocompatible polymer-free cubosomes for potential application in both PDT and bioimaging of skin malignant melanoma.

Topics: Cell Line, Tumor; Cell Proliferation; Cell Survival; Chlorophyllides; Drug Carriers; Glycerides; Humans; Kinetics; Liquid Crystals; Manganese; Melanoma; Melanoma, Cutaneous Malignant; Metalloporphyrins; Optical Imaging; Particle Size; Photochemotherapy; Photosensitizing Agents; Porphyrins; Propylene Glycol; Skin Neoplasms; Surface Properties