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Abstract：
Previously obtained amphiphilic graft copolymers based on [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA) ionic liquid were used as the matrices of three types of nanocarriers, i.e., conjugates with ionic piperacillin (PIP) and micelles with tazobactam (TAZ), which represented single systems, and dual systems bearing PIP anions and encapsulated TAZ for co-delivery. The exchange of Cl anions in TMAMA units with PIP ones resulted in a yield of 45.6-72.7 mol.%. The self-assembling properties were confirmed by the critical micelle concentration (CMC), which, after ion exchange, increased significantly (from 0.011-0.020 mg/mL to 0.041-0.073 mg/mL). The amphiphilic properties were beneficial for TAZ encapsulation to reach drug loading contents (DLCs) in the ranges of 37.2-69.5 mol.% and 50.4-80.4 mol.% and to form particles with sizes of 97-319 nm and 24-192 nm in the single and dual systems, respectively. In vitro studies indicated that the ionically conjugated drug (PIP) was released in quantities of 66-81% (7.8-15.0 μg/mL) from single-drug systems and 21-25% (2.6-3.9 μg/mL) from dual-drug systems. The release of encapsulated TAZ was more efficient, achieving 47-98% (7.5-9.0 μg/mL) release from the single systems and 47-69% (9.6-10.4 μg/mL) release from the dual ones. Basic cytotoxicity studies showed non-toxicity of the polymer matrices, while the introduction of the selected drugs induced cytotoxicity against normal human bronchial epithelial cells (BEAS-2B) with the increase in concentration.
摘要：
先前获得的基于[2-（甲基丙烯酰氧基）乙基]三甲基氯化铵（TMAMA）离子液体的两亲性接枝共聚物被用作三种类型的纳米载体的基质，即，与离子型哌拉西林（PIP）的缀合物和与他唑巴坦（TAZ）的胶束，代表单一系统，和带有PIP阴离子和包封的TAZ的双系统用于共同递送。TMAMA单元中的Cl阴离子与PIP阴离子的交换导致45.6-72.7mol的产率。%.临界胶束浓度（CMC）证实了自组装性能，which,离子交换后，显着增加（从0.011-0.020mg/mL增加到0.041-0.073mg/mL）。两亲性质有利于TAZ包封达到37.2-69.5mol范围内的载药量(DLC)。%和50.4-80.4mol。％，并在单系统和双系统中形成大小为97-319nm和24-192nm的颗粒，分别。体外研究表明，离子缀合药物（PIP）从单药物系统中释放的量为66-81％（7.8-15.0μg/mL），从双药物系统中释放的量为21-25％（2.6-3.9μg/mL）。封装的TAZ的释放更有效，单系统释放47-98％（7.5-9.0μg/mL），双系统释放47-69％（9.6-10.4μg/mL）。基本的细胞毒性研究表明，聚合物基质无毒性，随着浓度的增加，所选药物的引入会诱导对正常人支气管上皮细胞（BEAS-2B）的细胞毒性。
