Structure-biocompatibility and transfection activity relationships of cationic polyaspartamides with (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups

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• 作者：Diana Salakhieva^a ; Vesta Shevchenko^a ; Csaba Né ; meth^b ; Benjá ; min Gyarmati^b ; Andrá ; s Szilá ; gyi^b ; ^{aszilagyi@mail.bme.hu} ; Timur Abdullin^a ; ^{tabdulli@gmail.com}
• 关键词：α-MEM ; minimum essential medium Eagle &ndash ; alpha modification ; B ; n-butylamine ; BSA ; bovine serum albumin ; CMC ; critical micelle concentration ; CPTA ; 3-(carboxypropyl)trimethyl-ammonium chloride ; DEAEMA ; (diethylamino)ethyl methacrylate ; DEE ; 2-(diethylamino)ethylamine ; DEP ; 3-(diethylamino)-1-propylamine ; DLS ; dynamic light scattering ; DMEM ; Dulbecco&rsquo ; s modified Eagle&rsquo ; s medium ; DME ; 2-(dimethylamino)ethylamine ; DMF ; dimethylformamide ; DMP ; 3-(dimethylamino)-1-propylamine ; DMSO ; di
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：30 January 2017
• 年：2017
• 卷：517
• 期：1-2
• 页码：234-246
• 全文大小：1792 K
• 卷排序：517

文摘

A series of 14 cationic derivatives of poly(aspartic acid) i.e. cationic polyaspartamides with different (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups was synthesized by nucleophilic addition on polysuccinimide. The resulting polyaspartamides have moderate amphiphilic properties. Relationships between the structure and ratio of side groups and in vitro properties of polyaspartamides, including their cytotoxic and membrane-damaging activity towards human cell lines, primary skin fibroblasts and erythrocytes, were established and discussed. Cationic polyaspartamides vary in their DNA-binding, condensing and nuclease-protecting characteristics depending on the concentration ratio of (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups. Effective cell transfection was achieved upon polyaspartamide-mediated plasmid DNA delivery in serum-free medium in the presence of chloroquine. Effect of serum proteins adsorption onto polyaspartamide based polyplexes, and the role of concentration of polyplexes in culture medium in their colloidal stability and transfection process were demonstrated. Synthesized polyaspartamides are biocompatible and long-acting gene carriers, which are applied to cells after dilution and without washing, thus providing transfection level comparable to that of commercial transfection reagent.