Paclitaxel-Loaded Poly(-glutamic acid)-poly(lactide) Nanoparticles as a Targeted Drug Delivery System against Cultured HepG2 Cells
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- 作者：Hsiang-Fa Liang ; Sung-Ching Chen ; Mei-Chin Chen ; Po-Wei Lee ; Chiung-Tong Chen ; and Hsing-Wen Sung
- 刊名：Bioconjugate Chemistry
- 出版年：2006
- 出版时间：March 2006
- 年：2006
- 卷：17
- 期：2
- 页码：291 - 299
- 全文大小：684K
- 年卷期：v.17,no.2(March 2006)
- ISSN：1520-4812
文摘
The study was to develop paclitaxel-loaded formulations using a novel type of self-assembled nanoparticles thatwas composed of block copolymers synthesized from poly(
-glutamic acid) and poly(lactide) via a simple couplingreaction. The nanoparticles (the NPs) were prepared with various feed weight ratios of paclitaxel to block copolymer(the P/BC ratio). The morphology of all prepared nanoparticles was spherical and the surfaces were smooth.Increasing the P/BC ratio significantly increased the drug loading content of the prepared nanoparticles, butremarkably reduced the drug loading efficiency. The release rate of paclitaxel from the NPs decreased significantlyas the P/BC ratio increased. For the potential of targeting liver cancer cells, galactosamine was further conjugatedon the prepared nanoparticles (the Gal-NPs) as a targeting moiety. It was found that the activity in inhibiting thegrowth of HepG2 cells (a liver cancer cell line) by the Gal-NPs was comparable to that of a clinically availablepaclitaxel formulation, while the NPs displayed a significantly less activity. This may be attributed to the factthat the Gal-NPs had a specific interaction with HepG2 cells via ligand-receptor recognition. Cells treated withdistinct paclitaxel formulations resulted in arrest in the G2/M phase. The arrest of cells in the G2/M phase washighly suggestive of interference by paclitaxel with spindle formation and was consistent with the morphologicalfindings presented herein. In conclusion, the active targeting nature of the Gal-NPs prepared in the study may beused as a potential drug delivery system for the targeted delivery to liver cancers.
-glutamic acid) and poly(lactide) via a simple couplingreaction. The nanoparticles (the NPs) were prepared with various feed weight ratios of paclitaxel to block copolymer(the P/BC ratio). The morphology of all prepared nanoparticles was spherical and the surfaces were smooth.Increasing the P/BC ratio significantly increased the drug loading content of the prepared nanoparticles, butremarkably reduced the drug loading efficiency. The release rate of paclitaxel from the NPs decreased significantlyas the P/BC ratio increased. For the potential of targeting liver cancer cells, galactosamine was further conjugatedon the prepared nanoparticles (the Gal-NPs) as a targeting moiety. It was found that the activity in inhibiting thegrowth of HepG2 cells (a liver cancer cell line) by the Gal-NPs was comparable to that of a clinically availablepaclitaxel formulation, while the NPs displayed a significantly less activity. This may be attributed to the factthat the Gal-NPs had a specific interaction with HepG2 cells via ligand-receptor recognition. Cells treated withdistinct paclitaxel formulations resulted in arrest in the G2/M phase. The arrest of cells in the G2/M phase washighly suggestive of interference by paclitaxel with spindle formation and was consistent with the morphologicalfindings presented herein. In conclusion, the active targeting nature of the Gal-NPs prepared in the study may beused as a potential drug delivery system for the targeted delivery to liver cancers.