Dynamic intracellular delivery of antibiotics via pH-responsive polymersomes.
Dynamic intracellular delivery of antibiotics via pH-responsive polymersomes.
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DOI：
10.1039/c4py01249f
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发表时间：
2015-02-28
影响因子：
4.6
通讯作者：
Convertine AJ
中科院分区：
文献类型：
--
作者：
Lane DD;Su FY;Chiu DY;Srinivasan S;Wilson JT;Ratner DM;Stayton PS;Convertine AJ
采用可逆加成-断裂链转移（RAFT）聚合法制备了一系列由甲基丙烯酸羟乙酯（HEMA）和聚乙二醇甲醚甲基丙烯酸酯（FWavg ~ 950 Da）（O 950）组成的共聚物，这些共聚物具有不同的共聚单体组成和分子量，可用作聚合物支架。单体对的反应活性比分别测定为1.37和0.290。使用碳二亚胺化学将基于三硫代碳酸酯的RAFT链转移剂（CTA）接枝到这些支架。随后使用所得接枝链转移剂（gCTA）将甲基丙烯酸二甲氨基乙酯（DMAEMA）和（HPMA）在25和200的聚合度（DP）之间接枝。针对来自34臂接枝gCTA的DP为100的DMAEMA聚合的动力学分析显示线性Mn转化率和具有窄分子量分布的伪一级速率图，其随着单体转化率向较低洗脱体积移动。在单体转化率高达70%时，这些聚合反应的λ值保持在约1.20的低水平。pH值响应的endosomalytic刷能够自发自组装成聚合物囊泡的合成和动态光散射（DLS），cryoTEM，和红细胞溶血的组合，采用评估的聚合物刷的水溶液性质作为pH值的函数。成功封装头孢他啶和pH依赖性药物释放特性，通过HPLC确认。在感染B的巨噬细胞共培养模型中证实了载药聚合物囊泡的细胞内抗生素活性。thailandensis和RAW 264.7细胞。
Reversible addition-fragmentation chain transfer (RAFT) polymerization was employed to prepare a series of copolymers consisting of 2-hdroxyethyl methacrylate (HEMA) and poly(ethylene glycol) methyl ether methacrylate (FWavg ~ 950 Da) (O950) with variable comonomer compositions and molecular weights for use as polymeric scaffolds. Reactivity ratios for the monomer pair were determined to be 1.37 and 0.290 respectively. To these scaffolds trithiocarbonate-based RAFT chain transfer agents (CTAs) were grafted using carbodiimide chemistry. The resultant graft chain transfer agents (gCTA) were subsequently employed to polymerize dimethylaminoethyl methacrylate (DMAEMA) and (HPMA) between degrees of polymerization (DP) of 25 and 200. Kinetic analysis for the polymerization of DMAEMA targeting a DP of 100 from a 34 arm graft gCTA show linear Mn conversion and pseudo first order rate plots with narrow molecular weight distributions that move toward lower elution volumes with monomer conversion. Đ values for these polymerizations remain low at around 1.20 at monomer conversions as high as 70 %. pH-responsive endosomalytic brushes capable of spontaneously self-assembling into polymersomes were synthesized and a combination of dynamic light scattering (DLS), cryoTEM, and red blood cell hemolysis were employed to evaluate the aqueous solution properties of the polymeric brush as a function of pH. Successful encapsulation of ceftazidime and pH-dependent drug release properties were confirmed by HPLC. Intracellular antibiotic activity of the drug-loaded polymersomes was confirmed in a macrophage coculture model of infection with B. thailandensis and RAW 264.7 cells.