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]-trimethylammonium 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.