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.