title: Delivery platform for hydrophobic drugs: prodrug approach combined with self-assembled multilayers.
abstract: We report the design of a platform for the delivery of hydrophobic drugs via a macromolecular prodrug approach combined with LbL-assembled polyelectrolyte multilayers. A hyaluronan ester prodrug of the chemotherapeutic drug paclitaxel has been synthesized. Conjugation of the drug to hyaluronan through a labile succinate ester did not inhibit its activity. Using quartz crystal microbalance, atomic force microscopy, and UV spectroscopy, we have shown that the presence of the hydrophobic paclitaxel moieties does not prohibit the layer-by-layer construction of the multilayers. Release of the drug from the paclitaxel-loaded multilayers upon hydrolysis of the ester linkage resulted in a drastic cell death. Application of this delivery platform to substrates such as colloids, biomedical implants, or vascular tissues may lead to new therapeutic strategies.
authors.affiliation: Department of Biomedical Engineering, McGill University, H3A 2B Montreal, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Thierry
authors.forename: Piotr
authors.initials: P
authors.lastname: Kujawa
authors.forename: Cathy
authors.initials: C
authors.lastname: Tkaczyk
authors.forename: Françoise M
authors.initials: FM
authors.lastname: Winnik
authors.forename: Luc
authors.initials: L
authors.lastname: Bilodeau
authors.forename: Maryam
authors.initials: M
authors.lastname: Tabrizian
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011355:Prodrugs; D013386:Succinates / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D011355:Prodrugs; D013386:Succinates; D006820:Hyaluronic Acid; D048271:Chitosan; D017239:Paclitaxel