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

Tools

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

Repository Staff Only: item control page