Drug pH-Sensitive Release in Vitro and Targeting Ability of Polyamidoamine Dendrimer Complexes for Tumor Cells
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- Liu Dan
- School of Pharmacy, Shenyang Pharmaceutical University
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- Hu Haiyang
- School of Pharmacy, Shenyang Pharmaceutical University
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- Zhang Jie
- School of Pharmacy, Shenyang Pharmaceutical University
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- Zhao Xiuli
- School of Pharmacy, Shenyang Pharmaceutical University
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- Tang Xing
- School of Pharmacy, Shenyang Pharmaceutical University
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- Chen Dawei
- School of Pharmacy, Shenyang Pharmaceutical University
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Recently, dendrimers have been widely used in medical applications such as drug delivery and gene transfection. In this study, a pH-sensitive diblock copolymer of poly(methacryloyl sulfadimethoxine) (PSD) and polyethylene glycol (PEG) modified by lactose (LA-PEG-b-PSD) was synthesized. The pKa value of the LA-PEG-b-PSD was also measured. Then, polyamidoamine (PAMAM) complexes were prepared with PAMAM (G4.0) and LA-PEG-b-PSD by electrostatic interaction. To investigate drug pH-sensitive release in vitro, doxorubicin (DOX) was loaded in PAMAM. A higher drug cumulative release from LA-PEG-b-PSD/PAMAM complexes in phosphate buffered saline (PBS) was found at pH 6.5 than at pH 7.4. The cytotoxicity and cellular uptake of PAMAM complexes were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and confocal microscopy. LA-PEG-b-PSD/PAMAM/DOX complexes were able to enhance the cytotoxicity of DOX against HepG2 cells at pH 7.4. Confocal microscopy showed a higher cellular uptake of PEG-b-PSD/PAMAM complexes at pH 6.5. PAMAM complexes modified by lactose showed a higher affinity for hepatic cancer cells than those without lactose at pH 7.4. These results suggest that LA-PEG-b-PSD/PAMAM complexes exhibit selective targeting and cytotoxicity against HepG2 cells. In vivo antitumor studies showed that the LA-PEG-b-PSD/PAMAM/DOX complexes displayed higher antitumor efficacy compared with non-targeted PAMAM/DOX and DOX solution. These results indicate that this strategy should be applicable to the treatment of liver cancers.
収録刊行物
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- CHEMICAL & PHARMACEUTICAL BULLETIN
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CHEMICAL & PHARMACEUTICAL BULLETIN 59 (1), 63-71, 2011
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679150809088
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- NII論文ID
- 130000405490
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- NII書誌ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL書誌ID
- 10927253
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- 使用不可