ATRP-Synthesized Linear Copolymer Conjugates from Pharmaceutically Functionalized Choline Ionic Liquid Monomers for Ampicillin Delivery

Introduction: Linear polymer drug delivery through ATRP (atom transfer radical polymerization) stands as a breakthrough in medical science, offering exceptional advantages. The controlled and predictable structure of linear polymers ensures precisely regulated drug release, optimizing therapeutic outcomes. This method allows for tailored drug delivery, enabling the targeting of specific cells or tissues with minimal side effects.

Methods: This study involved the synthesis of monomeric ionic liquids by substituting the chloride counterion in [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA/Cl) with the ampicillin anion from its sodium salt (AMPNa), resulting in the formation of [2-(methacryloyloxy)ethyl]trimethylammonium ampicillin (TMAMA/AMP). Subsequently, methyl methacrylate (MMA) was copolymerized with TMAMA/AMP using the ATRP method, producing copolymers based on AMP, denoted as P(TMAMA/AMP-co-MMA). The drug release mechanism was facilitated by ion exchange with phosphate anions in PBS, mimicking the natural environment of physiological fluids with a pH of 3.7 at 37°C.

Results: The drug carriers exhibited 61–76% of the AMP contents in the copolymers. The polymeric chain lengths were determined by assessing the total monomer conversion (27–47%), leading to a degree of polymerization (DPn = 131-363). Utilizing dynamic light scattering (DLS), the hydrodynamic diameters (Dh = 190–328 nm) of polymer nanoparticles and their polydispersity index (PDI = 0.01-0.06) in an aqueous solution were determined. In addition, in vitro studies demonstrated the release of 72–100% (11.1–19.5 µg/mL) of drug within 26 hours.

Conclusion: Our study explored the well-defined linear copolymers, P(TMAMA/AMP-co-MMA)s, with varying ionic contents, showcasing their promise as carriers in drug delivery systems (DDS). The findings affirm the efficacy of the trimethylammonium-based IL monomer carrying AMP in designing polymeric carriers with precise amounts of therapeutically active anion. This DDS holds potential for preventing and treating diverse bacterial infections, including respiratory tract infections.