Abstract |
To improve the water solubility of the anticancer drug candidate LCTA-2034 (A1), we investigated the formation of complexes of this anthrax[2,3-b] furan congener with the solubilizing 2-hydroxypropyl derivative of β- cyclodextrin HP-βCD (Cavitron®). The interaction of A1 with HP-βCD resulted in the inclusion complex A1/HP-βCD in 1:1 stoichiometry. The A1/HP-βCD complex was used to develop a prototype of a lyophilised drug formulation with enhanced (>10-fold) aqueous solubility than A1 and a long-term stability. The use of HP-βCD decreased the acute toxicity of A1 by >30%. The A1/HP-βCD drug formulation as well as A1 in equal doses (5×30mg/kg) to increase the lifespan by up to 140% for mice with i.p. transplanted P388 leukaemia. Furthermore, the A1/HP-βCD formulation demonstrated a significant and reliable antitumor efficacy in a Р388/ADR drug resistant leukaemia and B16/F10 melanoma, proving a perspective of investigations of toxicology, biodistribution and pharmacokinetics.
|
Authors | Helen M Treshalina, Vladimir I Romanenko, Dmitry N Kaluzhny, Michael I Treshalin, Aleksey A Nikitin, Alexander S Tikhomirov, Andrey E Shchekotikhin |
Journal | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
(Eur J Pharm Sci)
Vol. 109
Pg. 631-637
(Nov 15 2017)
ISSN: 1879-0720 [Electronic] Netherlands |
PMID | 28927751
(Publication Type: Journal Article)
|
Copyright | Copyright © 2017 Elsevier B.V. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Furans
- LCTA-2034
- 2-Hydroxypropyl-beta-cyclodextrin
|
Topics |
- 2-Hydroxypropyl-beta-cyclodextrin
(chemistry, pharmacology, therapeutic use, toxicity)
- Animals
- Antineoplastic Agents
(chemistry, pharmacology, therapeutic use, toxicity)
- Cell Survival
(drug effects)
- Drug Resistance, Neoplasm
- Female
- Furans
(chemistry, pharmacology, therapeutic use, toxicity)
- HCT116 Cells
- Humans
- Lethal Dose 50
- Leukemia
(drug therapy)
- Melanoma, Experimental
(drug therapy)
- Mice, Inbred C57BL
- Mice, Inbred DBA
|