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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.; 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, Vol. 27, No. 4: p. 173


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.