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| Item Type: | Article |
|---|---|
| Title: | Improving topical non-melanoma skin cancer treatment: In vitro efficacy of a novel guanosine-analog phosphonate |
| Creators Name: | Ali-von Laue, C., Zoschke, C., Do, N., Lehnen, D., Küchler, S., Mehnert, W., Blaschke, T., Kramer, K.D., Plendl, J., Weindl, G., Korting, H.C., Hoeller Obrigkeit, D., Merk, H.F. and Schäfer-Korting, M. |
| 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. |
| Keywords: | Drug Delivery Systems, Keratin-18, Preclinical Drug Development, Purine Nucleotide Analogues, Tissue Engineering, Topical Administration, Non-Melanoma Skin Cancer, Animals |
| Source: | Skin Pharmacology and Physiology |
| ISSN: | 1660-5527 |
| Publisher: | Karger |
| Volume: | 27 |
| Number: | 4 |
| Page Range: | 173 |
| Date: | May 2014 |
| Official Publication: | https://doi.org/10.1159/000354118 |
| PubMed: | View item in PubMed |
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