Liposomal formulations of Etoposide and Docetaxel for p53 mediated enhanced cytotoxicity in lung cancer cell lines.

Autor: Jinturkar KA; Pharmacy Department, Faculty of Technology & Engineering, The Maharaja Sayajirao University of Baroda, Post Box No.: 51, Kalabhavan, Vadodara 390 001, Gujarat state, India., Anish C, Kumar MK, Bagchi T, Panda AK, Misra AR
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2012 Mar; Vol. 33 (8), pp. 2492-507. Date of Electronic Publication: 2011 Dec 24.
DOI: 10.1016/j.biomaterials.2011.11.067
Abstrakt: The objective of present investigation was to develop and assess comparative enhancement in cytotoxicity of liposomal Etoposide and Docetaxel in non-small cell lung cancer cell lines after pre-treatment and co-administration of p53 tumor suppressor gene and to assess direct lung targeting of optimized formulations by dry powder inhaler technology. Cationic liposomes with and without drug were prepared and allowed to form p53-lipoplex for undertaking cytotoxicity studies in H-1299 (p53 null) and A-549 (p53 wt) cell lines. The optimized lipoplexes showed average size of 200-350 nm, zeta potential of 25-32 mV and sustained drug release up to 16-24 h. The developed liposomes and lipoplexes showed significant intracellular uptake and demonstrated enhanced cytotoxicity of 13-28 % after p53-drug co-administration and 41-63 % after p53 pre-treatment. The p53 mediated enhanced cytotoxicity by increased apoptosis and necrosis was also confirmed using Annexin V - FITC assay. The increased apoptosis suggested restored p53 function and reduced anti-apoptotic drug resistance theirby causing cell sensitization and synergism towards cytotoxicity. The studies conducted above demonstrated significant cell chemo-sensitization after p53 pre-treatment followed by Etoposide/Docetaxel liposomes administration than p53-Etoposide or p53-Docetaxel lipoplex co-administration; more significantly in Docetaxel and in H 1299 cell line. All the formulations when developed as dry powder inhalers showed significant in vitro lung deposition pattern in cascade impactor with fine particle faction of 33-37%. The study opens up a new strategy to treat lung cancer especially in cases of drug resistance. Moreover direct delivery to lung may provide an important role in complete remission of the disease due to target specificity.
(Copyright © 2011 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: