Polyelectrolyte multilayer nanoshells with hydrophobic nanodomains for delivery of Paclitaxel

JOURNAL OF CONTROLLED RELEASE

卷:159

Article

Boudou, Thomas^1,2  Kharkar, Prathamesh^1,2  Jing, Jing³  Guillot, Raphael^1,2  Pignot-Paintrand, Isabelle³  Auzely-Velty, Rachel³  Picart, Catherine^1,2 

[1] Grenoble Inst Technol, F-38016 Grenoble, France

[2] CNRS, UMR 5628, LMGP, F-38016 Grenoble, France

[3] Univ Grenoble 1, Ctr Rech Macromol Vegetales CERMAV CNRS, Grenoble, France

关键词: Polysaccharides;    Hydrophobic drug delivery;    Paclitaxel;    Layer-by-layer film;    Biodegradability;    Breast cancer;   

DOI  :  10.1016/j.jconrel.2012.01.022

来源: Elsevier

【 摘 要 】

Efficient and effective delivery of poorly water-soluble drug molecules, which constitute a large part of commercially available drugs, is a major challenge in the field of drug delivery. Several drugs including paclitaxel (PTX) which are used for cancer treatment are hydrophobic, exhibit poor aqueous solubility and need to be delivered using an appropriate carrier. In the present work, we engineered PTX-loaded polyelectrolyte films and microcapsules by pre-complexing PTX with chemically modified derivative of hyaluronic acid (alkylamino hydrazide) containing hydrophobic nanocavities, and subsequent assembly with either poly(L-lysine) (PLL) or quaternized chitosan (QCHI) as polycations. The PTX loading capacity of the films was found to be dependent on number of layers in the films as well as on the initial concentration of PTX pre-complexed to hydrophobic HA, with a loading capacity up to 5000-fold the initial PTX concentration. The films were stable in physiological medium and were degraded in the presence of hyaluronidase. The PTX-loaded microcapsules were found to decrease the viability and proliferation of MDA MB 231 breast cancer cells, while unloaded microcapsules did not impact cell viability. All together, our results highlight the potential of hyaluronan-based assemblies containing hydrophobic nanodomains for hydrophobic drug delivery. (C) 2012 Elsevier B.V. All rights reserved.

【 授权许可】

Free