Delivery platform for hydrophobic drugs: prodrug approach combined with self-assembled multilayers.
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.
Thierry
Benjamin
B
Department of Biomedical Engineering, McGill University, H3A 2B Montreal, Canada.
Kujawa
Piotr
P
Tkaczyk
Cathy
C
Winnik
Françoise M
FM
Bilodeau
Luc
L
Tabrizian
Maryam
M
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
D011355:Prodrugs; D013386:Succinates; D006820:Hyaluronic Acid; D048271:Chitosan; D017239:Paclitaxel