Keihankhadiv Shadi, Neugebauer Dorota
Department of Physical Chemistry and Technology of Polymers, Faculty of Chemistry, Silesian University of Technology, 44-100 Gliwice, Poland.
Molecules. 2024 Dec 18;29(24):5973. doi: 10.3390/molecules29245973.
Single and dual-drug delivery systems (DDSs) based on linear choline polymers were designed through the controlled polymerization of a pharmaceutically functionalized monomer, i.e., [2-(methacryloyloxy)ethyl]trimethylammonium, with counterions of cloxacillin (TMAMA/CLX), or its copolymerization with [2-(methacryloyloxy)ethyl]trimethylammonium with ampicillin (TMAMA/AMP), providing antibiotic properties. This strategy was effective in attaining well-defined linear copolymers with 38-93 mol. % of TMAMA content, which were regulated by the initial ratio of TMAMA to methyl methacrylate comonomer. The polymer compositions were controlled by the total monomer conversion (40-75%), resulting in a variable degree of polymerization (DP = 160-300) and pharmaceutical anion contents (CLX 51-80% and AMP 78-87%). In aqueous solution, the polymers formed particles with sizes ranging between 274 and 380 nm for CLX systems and 288-348 nm for CLX/AMP systems. In vitro drug release, driven by the exchange of pharmaceutical anions with phosphate ions in phosphate-buffered saline (PBS), imitating a physiological fluid, demonstrated release efficiencies of 58-76% for CLX (10.5-13.6 µg/mL) in single systems, and 91-100% for CLX (12.9-15.1 µg/mL) and 97-100% for AMP (21.1-23.3 µg/mL) in dual systems. Compared to conventional systems delivering antibiotics without a polymer carrier, the choline-based polymer DDS attained satisfactory levels of drug loading content and (co-)release from the polymer carriers, offering a promising alternative for antibiotic delivery.
基于线性胆碱聚合物的单药和双药递送系统（DDS）是通过对一种药物功能化单体，即[2-(甲基丙烯酰氧基)乙基]三甲基铵，与氯唑西林（TMAMA/CLX）的抗衡离子进行可控聚合，或使其与[2-(甲基丙烯酰氧基)乙基]三甲基铵与氨苄西林（TMAMA/AMP）进行共聚而设计的，从而具备抗生素特性。该策略有效地获得了具有38 - 93摩尔% TMAMA含量的明确线性共聚物，其含量由TMAMA与甲基丙烯酸甲酯共聚单体的初始比例调节。聚合物组成由总单体转化率（40 - 75%）控制，导致聚合度可变（DP = 160 - 300）以及药物阴离子含量可变（CLX为51 - 80%，AMP为78 - 87%）。在水溶液中，对于CLX系统，聚合物形成的颗粒尺寸在274至380纳米之间，对于CLX/AMP系统，颗粒尺寸在288 - 348纳米之间。在体外药物释放实验中，在模拟生理流体的磷酸盐缓冲盐水（PBS）中，药物阴离子与磷酸根离子交换驱动释放，单系统中CLX（10.5 - 13.6 µg/mL）的释放效率为58 - 76%，双系统中CLX（12.9 - 15.1 µg/mL）的释放效率为91 - 100%，AMP（21.1 - 23.3 µg/mL）的释放效率为97 - 100%。与没有聚合物载体递送抗生素的传统系统相比，基于胆碱的聚合物DDS在聚合物载体中的药物负载量和（共）释放方面达到了令人满意的水平，为抗生素递送提供了一种有前景的替代方案。
