Dual-Drug Delivery via the Self-Assembled Conjugates of Choline-Functionalized Graft Copolymers

Graft copolymers based on a choline ionic liquid (IL), [2-(methacryloyloxy)ethyl]-trimethyl-ammonium 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.