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
