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- Title
Tumor-targeting and redox-sensitive micelles based on hyaluronic acid conjugate for delivery of paclitaxel.
- Authors
Liu, Jiyang; Liang, Na; Li, Shupeng; Han, Yang; Yan, Pengfei; Kawashima, Yoshiaki; Cui, Fude; Sun, Shaoping
- Abstract
The clinical application of paclitaxel is limited due to its low solubility and severe side effects. A tumor-targeting and redox-sensitive paclitaxel-loaded micellar system could exhibit high drug solubility, excellent antitumor activity and low toxicity to normal tissues. An mPEG and hexadecanol-modified hyaluronic acid with disulfide bridges in the molecules (mPEG-S-S-HA-C16) was designed and synthesized. Using mPEG-S-S-HA-C16 as the carrier, the paclitaxel-loaded micelles were fabricated, and their physicochemical properties were studied deeply. Moreover, the antitumor evaluation of the paclitaxel-loaded micelles was conducted in vitro and in vivo. For the optimized paclitaxel-loaded mPEG-S-S-HA-C16 micelles, the average size and zeta potential were 168.6 nm and −38.2 mV, respectively. In vitro drug release study demonstrated the redox-sensitivity of the micelles that the encapsulated paclitaxel could be released rapidly in the presence of glutathione. MTT assay confirmed the low toxicity of the polymeric material itself and the excellent cytotoxicity of paclitaxel-loaded mPEG-S-S-HA-C16 micelles against MCF-7 cells. Moreover, the in vivo antitumor evaluation demonstrated the superior antitumor efficacy of the paclitaxel-loaded micelles. These results suggested that the paclitaxel-loaded mPEG-S-S-HA-C16 micelles held great promise for targeted delivery of paclitaxel.
- Subjects
HYALURONIC acid; PACLITAXEL; MICELLES; DRUG solubility; ZETA potential; DRUG side effects
- Publication
Journal of Biomaterials Applications, 2020, Vol 34, Issue 10, p1458
- ISSN
0885-3282
- Publication type
Article
- DOI
10.1177/0885328220905256