Cross-Linked Nanoassemblies from Poly(ethylene glycol)-poly(aspartate) Block Copolymers as Stable Supramolecular Templates for Particulate Drug Delivery
Cross-Linked Nanoassemblies from Poly(ethylene glycol)-poly(aspartate) Block Copolymers as Stable Supramolecular Templates for Particulate Drug Delivery
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DOI：
10.1021/bm200483t
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发表时间：
2011-07-01
影响因子：
6.2
通讯作者：
Bae, Younsoo
中科院分区：
文献类型：
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作者：
Lee, Hyun Jin;Bae, Younsoo
嵌段共聚交联型纳米组件(CNAs)被开发为稳定的超分子模板，用于微粒药物的输送。聚乙二醇聚天冬氨酸[PEGp(Asp)]嵌段共聚物由聚乙二醇(5 kDa或12 kDa)和天冬氨酸(Asp)(5，14，25，33和37个重复单元)组成，作为支架和接枝物，制备了接枝纳米组装件(GNA)和CNAs的纳米组装库。测试了四条合成路线，以最大限度地增加每个纳米组装的药物结合天冬氨酸单位的数量。GNA的合成采用支架接枝法和支架接枝法。将部分或完全脱保护的聚乙二醇-p(天冬氨酸)与二胺类化合物进行交联，制备了纳米碳纳材料。H-1NMR和GPC测量表明，GNAS和CNAS分别含有最大的183和253个Asp单位。对纳米组件的初步筛选表明，由于不同的接枝效率和低的产品产量，GNAS作为药物载体的进一步发展将是不切实际的。CNAs是一种高产率的超分子模板，可以包裹和释放可电离药物(阿霉素)，在与药物相关的pH范围内提高了纳米组合物的粒子稳定性。光散射测量表明，CNAs在药物包埋前后的粒径保持一致，既不引起聚集，也不引起解离(
Block copolymer cross-linked nanoassemblies (CNAs) were developed as stable supramolecular templates for particulate drug delivery. Poly(ethylene glycol)-poly(aspartate) [PEG-p(Asp)] block copolymers, consisting of PEG (5 or 12 kDa) and Asp (5, 14, 25, 33, and 37 repeating units), were used as scaffolds and grafts in combination to prepare a nanoassembly library of grafted nanoassemblies (GNAs) and CNAs. Four synthesis routes were tested to maximize the number of drug-binding Asp units per nanoassembly. Grafting-onto-scaffold and grafting-from-scaffold methods were used for GNA synthesis. Either partially or completely deprotected PEG-p(Asp) was cross-linked with diamine compounds to prepare CNAs. H-1 NMR and GPC measurements showed that GNAs and CNAs contained the maximum 183 and 253 Asp units, respectively. Initial screening of the nanoassemblies revealed that GNAs would be impractical for further development as drug carriers due to variable grafting efficiency and low product yields. CNAs were obtained in high yields and identified as a promising supramolecular template that can entrap and release ionizable drugs (doxorubicin), enhancing the particle stability of nanoassemblies in the pharmaceutically relevant pH ranges between 4 and 9. Light scattering measurements demonstrated that the particle size of CNAs remained uniform before and after drug entrapment, causing neither aggregation nor dissociation (