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

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. and Zoschke, C. and Do, N. and Lehnen, D. and Küchler, S. and Mehnert, W. and Blaschke, T. and Kramer, K.D. and Plendl, J. and Weindl, G. and Korting, H.C. and Hoeller Obrigkeit, D. and 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

Repository Staff Only: item control page