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.
Eine Methode zur Herstellung großer Volumen von sterilen, homoge-nen unilamellaren Liposomen als Träger von lipophilen Cytosinarabi-nosid(Ara-C)- und Fluorodeoxyuridin (FUdR)-Derivaten (Prodrugs) wird beschrieben. Die Methode beruht auf der Dialyse von Lipid/ Prodrug/Detergens-Mizellen mittels Kapillardialyse. Es entstehen Liposomen im Größenbereich von 60–120 Nanometern mit quantitati-vem Einbau der Prodrugs. Die zytostatische Wirkung von Ara-C-Prodrug-Liposomen gegen L1210-Leukämie ist dem freien Ara-C deutlich überlegen, wobei die Dosis um das 10–20fache reduziert werden kann. Die FUdR-Prodrug-Liposomen zeigen gegen verschiedene Tumoren (Lewis Lung, Mammakarzinom M13/C, L1210 und Kolon C38) eben-falls eine zytostatische Wirkung, die jedoch verglichen mit den Ara-C-Prodrug-Liposomen weniger ausgeprägt ist. Mit der Kopplung von tumorzellspezifischen Antikörpern an solche Prodrug-Liposomen kann durch spezifische Bindung an die Tumorzel-len («drug targeting») der zytostatische Effekt möglicherweise weiter verbessert und gleichzeitig die systemische Toxizität der Zytostatika reduziert werden.
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