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KMID : 1094720200250020224
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Biotechnology and Bioprocess Engineering
2020 Volume.25 No. 2 p.224 ~ p.234
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Effective Elimination of Charge-associated Toxicity of Low Generation Polyamidoamine Dendrimer Eases Drug Delivery of Oxaliplatin
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Do Vo Minh Hoang
Bach Long Giang
Tran Diem-Huong Nguyen
Cao Van Du
Nguyen Thi Nhu Quynh
Hoang Duc Thuan
Ngo Van Cuong
Nguyen Dai Hai
Thi Thai Thanh Hoang
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Abstract
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Polyamidoamine (PAMAM) dendrimer is emerging as an effective nanocarrier for delivering anticancer drugs. Still, unmodified PAMAM dendrimer is hardly used in vivo because of unsatisfied drug release, high tendency of interfering with cellular membranes, and rapid clearance by reticuloendothelial system. In this study, low generation polyamidoamine (PAMAM) dendrimer G3.0 is developed and surface modified with methoxypolyethylene glycol (PAMAM G3.0-mPEG) to overcome its limitations. Specifically, PAMAM G3.0 conjugated with mPEG at different ratios are investigated to effectively eliminate its charge-associated toxicity, in which PAMAM G3.0-mPEG- 8 is chosen for oxaliplatin (OX) loading. Results reveal that OX-loaded PAMAM G3.0-mPEG-8 has desirable size, good entrapment efficiency, and sustained release with minimum drug leakage. In addition, Resazurin assay indicates that the toxicity of loaded OX is reduced as compared to free drug but still maintain substantially anticancer activity on HeLa cells, suggesting the potential application of PAMAM G3.0-mPEG-8 for OX delivery in cancer therapy.
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KEYWORD
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polyamidoamine (PAMAM) dendrimer, oxaliplatin, low charge-associated toxicity, drug delivery systems, cancer therapy
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