title: Improving topical non-melanoma skin cancer treatment: In vitro efficacy of a novel guanosine-analog phosphonate.
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.
authors: Institute for Pharmacy, Freie Universität Berlin, Berlin, Germany.
authors: C
authors: C
authors: Ali-von Laue
authors: C
authors: C
authors: Zoschke
authors: N
authors: N
authors: Do
authors: D
authors: D
authors: Lehnen
authors: S
authors: S
authors: Küchler
authors: W
authors: W
authors: Mehnert
authors: T
authors: T
authors: Blaschke
authors: K D
authors: KD
authors: Kramer
authors: J
authors: J
authors: Plendl
authors: G
authors: G
authors: Weindl
authors: H C
authors: HC
authors: Korting
authors: D
authors: D
authors: Hoeller Obrigkeit
authors: H-F
authors: HF
authors: Merk
authors: M
authors: M
authors: Schäfer-Korting
mesh_terms: D000287:Administration, Topical; D000818:Animals; D016503:Drug Delivery Systems; D006151:Guanosine / Q000031:analogs & derivatives*; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage; D063065:Organophosphonates / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000188:drug therapy*; D023822:Tissue Engineering
chemical_list: D063065:Organophosphonates; D006151:Guanosine