title: Sebaceous-gland deposition of isotretinoin after topical application: an in vitro study using human facial skin.
abstract: As yet, topically applied isotretinoin fails to show convincing clinical efficacy in the treatment of severe recalcitrant acne. Although the reason for this is not known, it is possible that topical application results in low, pharmacologically inactive isotretinoin concentrations in the sebaceous glands, the most likely site of isotretinoin action. It has been suggested that topically applied liposomes enhance the delivery of drugs into the sebaceous glands. Accordingly, we compared the isotretinoin concentration in sebaceous glands and other skin compartments following topical application of small unilamellar vesicles, multilamellar vesicles, preformed vesicles (Natipide II) or mixed micelles of lecithin and bile salt. We found that the concentration of isotretinoin measured in the sebaceous glands varied between 0.17 and 1.57 ng/mg tissue. The comparison between ethanolic gel and liposomal or micellar gel did not reveal any significant difference. However, application of the Natipide formulation resulted in significantly lower isotretinoin concentrations in the sebaceous glands when compared to the ethanolic gel. Autoradiography and fluorescence microscopy indicated that isotretinoin penetrated the sebaceous glands along the follicular route. In conclusion, our in vitro study showed that, following topical administration, substantial amounts of isotretinoin were delivered to the sebaceous glands via the follicular route, whereby the ethanolic gel was as efficient as a liposomal or a mixed micellar gel.
authors.affiliation: Drug Delivery Systems Section, F. Hoffmann-La Roche AG, Basel, Switzerland. Thomas. Tschan@roche.com
authors.forename: T
authors.initials: T
authors.lastname: Tschan
authors.forename: H
authors.initials: H
authors.lastname: Steffen
authors.forename: A
authors.initials: A
authors.lastname: Supersaxo
mesh_terms: D000287:Administration, Topical; D001345:Autoradiography; D004337:Drug Carriers; D005145:Face; D005260:Female; D005782:Gels; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015474:Isotretinoin / Q000008:administration & dosage / Q000378:metabolism*; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000378:metabolism*; D008081:Liposomes; D008823:Micelles; D008856:Microscopy, Fluorescence; D012627:Sebaceous Glands / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: D004337:Drug Carriers; D005782:Gels; D007641:Keratolytic Agents; D008081:Liposomes; D008823:Micelles; D015474:Isotretinoin