聚合物-药物结合物的合成和表征 通过应变促进的化-基循环添加-介导的聚合
Omotola D Gbadegesin1, Simeon K Adesina1
1Department of Pharmaceutical Sciences, Howard University, Washington DC, USA.
概括
我们开发了用于向癌症治疗的新型聚合物药物合物 (PDC). 这种方法可以有效地合成高分子量PDCs,具有高药物负载,用于选择性输送抗癌剂.
科学领域:
- 聚合物化学 聚合物化学
- 药物运输 药物运输 药物运输
- 纳米医学是一种纳米医学.
背景情况:
- 聚合物-药物合物 (PDC) 通过改变其生物分布,对提高抗癌药物的疗效和安全性至关重要.
- 目标外的不良影响仍然是传统小分子抗癌药物的挑战.
研究的目的:
- 通过无催化剂,无高温聚合方法合成新型聚合物-药物联合体 (PDC).
- 为了实现高分子量PDC,具有高药物负载和狭窄的分子量分布.
- 评估药物释放机制和选择性药物输送的潜力.
主要方法:
- 应变促进的 [3 + 2] 亚酸环添加介导的渐进增长聚合被采用.
- 合成α-ω-bis-azide终结的单体,并通过cathepsin B-敏感链体 (GFLG) 与凝胺或多克索鲁结合.
- 用双功能聚乙烯糖单体的二子环氧化物聚合.
主要成果:
- 快速合成高分子量PDCs (gemcitabine~40.18 kDa,多克索鲁比辛~1800 kDa) 具有狭窄的分子量分布.
- 达到高药物负载:29.2%的重量. 杰姆西塔宾和10.3%的重量 德克索鲁比辛 (doxorubicin) 是一种可以
- 在初步的体外研究中,在pH 5.0下证明了cathepsin B催化药物释放.
结论:
- 开发的聚合法使PDCs的高效和选择性合成成为可能.
- 这些PDC显示出有潜力提供强效抗癌剂的向输送,最大限度地减少非向效应.
- 这项研究强调了一种开发先进癌症治疗方法的有希望的方法.
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