Improving topical non-melanoma skin cancer treatment: In vitro efficacy of a novel guanosine-analog phosphonate.
Skin Pharmacol Physiol
; 27(4): 173, 2014.
Article
en En
| MEDLINE
| ID: mdl-24503861
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
/
Sistemas de Liberación de Medicamentos
/
Organofosfonatos
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Guanosina
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Skin Pharmacol Physiol
Asunto de la revista:
DERMATOLOGIA
/
FARMACOLOGIA
/
FISIOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Alemania