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

Abstract

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.

Photoresponse of new azo pyridine functionalized poly(2-hydroxyethyl methacrylate-co-methyl methacrylate)

“…HEMA can be either polymerized or copolymerized to modify the properties of the resulting polymer. Furthermore, the available hydroxyl groups in the (co)polymer chain offer opportunity for the functionalization reactions including protection group or esterification, which leads to the preparation of activated bromides, so-called multifunctional macroinitiators used in ATRP (atom transfer radical polymerization) 28 – 30 . Therefore, advanced functional copolymers, e.g.…”

Piperacillin/Tazobactam Co-Delivery by Micellar Ionic Conjugate Systems Carrying Pharmaceutical Anions and Encapsulated Drug

“…The same drug has been successfully encapsulated and delivered by phosphonium PIL-based nanoparticles [ 30 ]. On the other hand, the more sophisticated structure of cholinium PIL-based graft copolymers is designed to carry p -aminosalicylate, clavulanate [ 31 ], cloxacillin [ 32 ], and fusidate [ 33 ].…”

“…For example, polymeric multi-branched IL-based chitosan nanocarriers for simultaneous delivery of doxorubicin and methotrexate have been reported [ 37 ]. Dual systems have also been studied by our group; the polymer carriers based on choline ionic liquid demonstrated successful delivery of salicylate and erythromycin [ 38 ], fusidate and rifampicin [ 33 ], and fusidate and cloxacillin [ 32 ] as pairs of drugs with a synergistic effect.…”

Synthesis and Characterization of Linear Copolymers Based on Pharmaceutically Functionalized Monomeric Choline Ionic Liquid for Delivery of p-Aminosalicylate

“…This monomer demonstrates potential in the synthesis of polymerized ionic liquids (PILs) [ 31 ], which are successful carriers for delivery of pharmaceutical anions. In other cases, the choline-based PILs acted as the universal matrices, where chloride anions were convenient to exchange with anionic drugs, such as sulfacetamide [ 32 ], p -aminosalicylate (PAS), fusidate, clavulanate, and piperaciline [ 33 , 34 , 35 , 36 ], to generate the pharmaceutically active polymeric systems. However, the choline-based PILs have been also prepared by polymerization of choline IL monomer with pharmaceutical anions, such as salicylate [ 31 , 37 , 38 ], fusidate, and cloxacillin.…”