Polymerizable Cholinium-Based Antibiotics for Polymer Carriers: Systems with Combined Load of Cloxacillin and Ampicillin

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_n = 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.