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|Title:||Targeted and intracellular delivery of paclitaxel using multi-functional polymeric micelles|
pH- and temperature-sensitive
Targeted and intracellular delivery
|Citation:||Seow, W.Y., Xue, J.M., Yang, Y.-Y. (2007-03). Targeted and intracellular delivery of paclitaxel using multi-functional polymeric micelles. Biomaterials 28 (9) : 1730-1740. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biomaterials.2006.11.039|
|Abstract:||Natural paclitaxel (Taxol®) is an effective anti-cancer drug, although a critical disadvantage is its non-targeting nature. To address this issue, cholesterol-grafted poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-co-undecenoic acid) was synthesized with different starting monomer ratios via a free radical copolymerization route. Folate was subsequently attached to the hydrophilic segment of the polymer in order to target folate receptors-overexpressing cancer cells. The success of synthesis was confirmed with 1H-NMR carried out in CDCl3/D2O. Using a membrane dialysis method, the polymer was then self-assembled into micelles whose hydrophobic cores could be utilized to encapsulate paclitaxel, an extremely hydrophobic compound. The polymer had a low CMC of ∼20 mg/L in water. Dynamic light scattering further showed that the sizes of blank micelles formed from the polymer were below 180 nm at different pH values tested and ∼220 nm upon drug incorporation. More importantly, it was demonstrated that the micelles exhibited a useful pH-induced thermo-sensitivity, such that drug was released more rapidly at pH 5.0 (acidic endosomal/lysosomal environment) than at pH 7.4 (normal extracellular pH). In vitro cytotoxicity assays performed against KB cells then provided concluding evidences that the cellular uptake of micelles surface-functionalised with folate was indeed enhanced due to a receptor-assisted endocytosis process. This novel polymeric design thus has the potential to be a useful paclitaxel vehicle for the treatment of folate-receptor positive cancers. © 2006 Elsevier Ltd. All rights reserved.|
|Appears in Collections:||Staff Publications|
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