Improving topical non-melanoma skin cancer treatment: In vitro efficacy of a novel guanosine-analog phosphonate

Ali-von Laue, C.; Zoschke, C.; Do, N.; Lehnen, D.; Kuchler, S.; Mehnert, W.; Blaschke, T.; Kramer, K. D.; Plendl, J.; Weindl, G.; Korting, H. C.; Hoeller Obrigkeit, D.; Merk, H.-F. und Schäfer-Korting, M. (2014): Improving topical non-melanoma skin cancer treatment: In vitro efficacy of a novel guanosine-analog phosphonate. In: Skin Pharmacology and Physiology, Bd. 27, Nr. 4: S. 173

Abstract

Actinic keratosis, a frequent carcinoma in situ of non-melanoma skin cancer (NMSC), can transform into life-threatening cutaneous squamous cell carcinoma. Current treatment is limited due to low complete clearance rates and asks for novel therapeutic concepts; the novel purine nucleotide analogue OxBu may be an option. In order to enhance skin penetration, solid lipid nanoparticles (SLN, 136-156 nm) were produced with an OxBu entrapment efficiency of 96.5 ± 0.1%. For improved preclinical evaluation, we combined tissue engineering with clinically used keratin-18 quantification. Three doses of 10(-3) mol/l OxBu, dissolved in phosphate-buffered saline as well as loaded to SLN, were effective on reconstructed NMSC. Tumour response and apoptosis induction were evaluated by an increase in caspase-cleaved fragment of keratin-18, caspase-7 activation as well as by reduced expression of matrix metallopeptidase-2 and Ki-67. OxBu efficacy was superior to equimolar 5-fluorouracil solution, and thus the drug should be subjected to the next step in preclinical evaluation.

• Dokumententyp: Zeitschriftenartikel
• Publikationsform: Publisher's Version
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1660-5527
• Allianz-/Nationallizenz: Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
• Sprache: Englisch