Polyelectrolyte multilayer nanoshells with hydrophobic nanodomains for delivery of Paclitaxel.
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.
Grenoble Institute of Technology and CNRS, UMR 5628, LMGP, 3 parvis Louis Néel, 38 016 Grenoble, France.
Thomas
T
Boudou
Grenoble Institute of Technology and CNRS, UMR 5628, LMGP, 3 parvis Louis Néel, 38 016 Grenoble, France.
Prathamesh
P
Kharkar
Centre de Recherches sur les Macromolécules Végétales (CERMAV-CNRS), affiliated with Université Joseph Fourier, and member of the Institut de Chimie Moléculaire de Grenoble, 601 rue de la piscine, Grenoble, France.
Jing
J
Jing
Grenoble Institute of Technology and CNRS, UMR 5628, LMGP, 3 parvis Louis Néel, 38 016 Grenoble, France.
Raphael
R
Guillot
Centre de Recherches sur les Macromolécules Végétales (CERMAV-CNRS), affiliated with Université Joseph Fourier, and member of the Institut de Chimie Moléculaire de Grenoble, 601 rue de la piscine, Grenoble, France.
Isabelle
I
Paintrand
Centre de Recherches sur les Macromolécules Végétales (CERMAV-CNRS), affiliated with Université Joseph Fourier, and member of the Institut de Chimie Moléculaire de Grenoble, 601 rue de la piscine, Grenoble, France.
Rachel
R
Auzely-Velty
Grenoble Institute of Technology and CNRS, UMR 5628, LMGP, 3 parvis Louis Néel, 38 016 Grenoble, France.
Catherine
C
Picart
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D057145:Nanoshells / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011073:Polyamines / Q000737:chemistry*; D000071228:Polyelectrolytes; D011107:Polylysine / Q000737:chemistry; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
D000972:Antineoplastic Agents, Phytogenic; D048271:Chitosan; D004337:Drug Carriers; D006820:Hyaluronic Acid; D017239:Paclitaxel; D011073:Polyamines; D000071228:Polyelectrolytes; D011107:Polylysine