Evaluation of triblock copolymeric micelles of δ- valerolactone and poly (ethylene glycol) as a competent vector for doxorubicin delivery against cancer

Journal of Nanobiotechnology

Research

Sankar Jagadeeshan¹  S Asha Nair¹  G S Vinod Kumar²  Lekha Nair K² 

[1] Cancer Research, Rajiv Gandhi Centre for Biotechnology, Poojappura, 695 014, Thiruvananthapuram, Kerala, India;Chemical Biology, Molecular Medicine Division, Rajiv Gandhi Centre for Biotechnology, Poojappura, 695 014, Thiruvananthapuram, Kerala, India;

关键词: Triblock Copolymer;    Polymeric Micelle;    U87MG Cell;    Ring Open Polymerization;    Copolymeric Micelle;   

DOI  :  10.1186/1477-3155-9-42

 received in 2011-04-20, accepted in 2011-09-25,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundSpecific properties of amphiphilic copolymeric micelles like small size, stability, biodegradability and prolonged biodistribution have projected them as promising vectors for drug delivery. To evaluate the potential of δ-valerolactone based micelles as carriers for drug delivery, a novel triblock amphiphilic copolymer poly(δ-valerolactone)/poly(ethylene glycol)/poly(δ-valerolactone) (VEV) was synthesized and characterized using IR, NMR, GPC, DTA and TGA. To evaluate VEV as a carrier for drug delivery, doxorubicin (DOX) entrapped VEV micelles (VEVDMs) were prepared and analyzed for in vitro antitumor activity.ResultsVEV copolymer was successfully synthesized by ring opening polymerization and the stable core shell structure of VEV micelles with a low critical micelle concentration was confirmed by proton NMR and fluorescence based method. Doxorubicin entrapped micelles (VEVDMs) prepared using a modified single emulsion method were obtained with a mean diameter of 90 nm and high encapsulation efficiency showing a pH dependent sustained doxorubicin release. Biological evaluation in breast adenocarcinoma (MCF7) and glioblastoma (U87MG) cells by flow cytometry showed 2-3 folds increase in cellular uptake of VEVDMs than free DOX. Block copolymer micelles without DOX were non cytotoxic in both the cell lines. As evaluated by the IC50 values VEVDMs induced 77.8, 71.2, 81.2% more cytotoxicity in MCF7 cells and 40.8, 72.6, 76% more cytotoxicity in U87MG cells than pristine DOX after 24, 48, 72 h treatment, respectively. Moreover, VEVDMs induced enhanced apoptosis than free DOX as indicated by higher shift in Annexin V-FITC fluorescence and better intensity of cleaved PARP. Even though, further studies are required to prove the efficacy of this formulation in vivo the comparable G2/M phase arrest induced by VEVDMs at half the concentration of free DOX confirmed the better antitumor efficacy of VEVDMs in vitro.ConclusionsOur studies clearly indicate that VEVDMs possess great therapeutic potential for long-term tumor suppression. Furthermore, our results launch VEV as a promising nanocarrier for an effective controlled drug delivery in cancer chemotherapy.

【 授权许可】

Unknown   
© Nair et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.