Intracellular delivery of paclitaxel using oil-free, shell cross-linked HSA - Multi-armed PEG nanocapsules

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Various approaches to increase the solubility of water-insoluble anti-cancer drugs in aqueous formulations have been undertaken with the aim of treating solid tumors through intravenous drug administration. Nanoscale drug carriers are particularly attractive for cancer therapy because of their passive targeting effect to enhance the therapeutic efficacy of drugs. Here we introduce an oil-free, shell crosslinked nanocapsule as an efficient intracellular delivery system for paclitaxel. The nanocapsules are prepared by emulsifying amine-reactive six-arm-branched polyethylene glycol (PEG) in dichloromethane into aqueous solution of human serum albumin (HSA), followed by cross-linking at the organic/aqueous interface. Paclitaxel is successfully incorporated into the HSA/PEG nanocapsules having a spherical shape with an average diameter of about 280 nm. In several types of cells, the surface modification of nanocapsules with a cell-penetrating peptide, Hph1, greatly facilitates cellular uptake and apoptosis-inducing effects of paclitaxel. Furthermore, the targeted anti-tumor activities of the paclitaxel-loaded nanocapsules in a mouse tumor model suggest that the shell cross-linked nanocapsules are very promising oil-free nanoscale delivery vehicles for water-insoluble anti-cancer agents. (C) 2011 Elsevier Ltd. All rights reserved.
Publisher
ELSEVIER SCI LTD
Issue Date
2011-11
Language
English
Article Type
Article
Keywords

HUMAN SERUM-ALBUMIN; CELL PENETRATING PEPTIDE; DRUG-DELIVERY; IN-VITRO; ANTITUMOR-ACTIVITY; NANOPARTICLES; CANCER; EFFICIENT; MICELLES; THERAPEUTICS

Citation

BIOMATERIALS, v.32, no.33, pp.8635 - 8644

ISSN
0142-9612
URI
http://hdl.handle.net/10203/99728
Appears in Collection
MS-Journal Papers(저널논문)
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