Niesyto Katarzyna, Mazur Aleksy, Neugebauer Dorota
Department of Physical Chemistry and Technology of Polymers, Faculty of Chemistry, Silesian University of Technology, 44-100 Gliwice, Poland.
Materials (Basel). 2022 Jun 24;15(13):4457. doi: 10.3390/ma15134457.
Graft copolymers based on a choline ionic liquid (IL), [2-(methacryloyloxy)ethyl]-trimethylammonium chloride (TMAMA), were obtained by atom transfer radical polymerization. The presence of chloride counterions in the trimethylammonium groups promoted anion exchange to introduce fusidate anions (FUS, 32−55 mol.%) as the pharmaceutical anions. Both the choline-based IL copolymers and their ionic drug-carrier conjugates (FUS systems as the first type, 26−208 nm) formed micellar structures (CMC = 0.011−0.025 mg/mL). The amphiphilic systems were advantageous for the encapsulation of rifampicin (RIF, 40−67 mol.%), a well-known antibiotic, resulting in single-drug (RIF systems as the second type, 40−95 nm) and dual-drug systems (FUS/RIF as the third type, 31−65 nm). The obtained systems released significant amounts of drugs (FUS > RIF), which could be adjusted by the content of ionic units and the length of the copolymer side chains. The dual-drug systems released 31−55% FUS (4.3−5.6 μg/mL) and 19−31% RIF (3.3−4.0 μg/mL), and these results were slightly lower than those for the single-drug systems, reaching 45−81% for FUS (3.8−8.2 μg/mL) and 20−37% for RIF (3.4−4.0 μg/mL). The designed polymer systems show potential as co-delivery systems for combined therapy against drug-resistant strains using two drugs in one formula instead of the separate delivery of two drugs.
通过原子转移自由基聚合制备了基于胆碱离子液体（IL）、[2-(甲基丙烯酰氧基)乙基]-三甲基氯化铵（TMAMA）的接枝共聚物。三甲基铵基团中氯离子抗衡离子的存在促进了阴离子交换，从而引入夫西地酸阴离子（FUS，32−55摩尔%）作为药物阴离子。基于胆碱的离子液体共聚物及其离子药物载体共轭物（第一类FUS系统，26−208纳米）均形成了胶束结构（临界胶束浓度=0.011−0.025毫克/毫升）。两亲性体系有利于包封著名抗生素利福平（RIF，40−67摩尔%），形成单药体系（第二类RIF系统，40−95纳米）和双药体系（第三类FUS/RIF，31−65纳米）。所制备的体系释放出大量药物（FUS>RIF），其释放量可通过离子单元含量和共聚物侧链长度进行调节。双药体系释放出31−55%的FUS（4.3−5.6微克/毫升）和19−31%的RIF（3.3−4.0微克/毫升），这些结果略低于单药体系，单药体系中FUS的释放量为45−81%（3.8−8.2微克/毫升），RIF的释放量为20−37%（3.4−4.0微克/毫升）。所设计的聚合物体系显示出作为联合治疗耐药菌株的共递送体系的潜力，该体系在一个配方中使用两种药物而不是分别递送两种药物。
