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

Jeong Yu Lee, Ki Hyun Bae, Jee Seon Kim, Yoon Sung Nam, Tae Gwan Park

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

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 cross-linked 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.

Original languageEnglish
Pages (from-to)8635-8644
Number of pages10
JournalBiomaterials
Volume32
Issue number33
DOIs
StatePublished - Nov 2011
Externally publishedYes

Funding

The late Professor Tae Gwan Park supervised the overall work as a principal investigator. All co-authors deeply appreciate his invaluable contribution and educational efforts. This research was financially supported from the Ministry of Health, Welfare and Family Affairs and the Ministry of Education, Science and Technology (Republic of Korea) through Basic Science Research Program (2010-0027955), the World Class University project, and the National Research Laboratory program. We thank Dr. Earl Choi and Prof. Won-il Jeong in the Graduate School of Medical Science and Engineering for their kind assistance in animal experiments.

FundersFunder number
World Class University
Ministry of Health and Welfare
Ministry of Education, Science and Technology2010-0027955

    Keywords

    • Cell-penetrating peptide
    • Drug delivery system
    • Human serum albumin
    • Nanocapsule
    • Paclitaxel

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