Pharmaceutical Functionalization of Monomeric Ionic Liquid for the Preparation of Ionic Graft Polymer Conjugates

Abstract

Polymerizable choline-based ionic liquid (IL), i.e., [2-(methacryloyloxy)ethyl]-trimethylammonium (TMAMA/Cl¯), was functionalized by an ion exchange reaction with pharmaceutical anions, i.e., cloxacillin (CLX¯) and fusidate (FUS¯), as the antibacterial agents. The modified biocompatible IL monomers (TMAMA/CLX¯, TMAMA/FUS¯) were copolymerized with methyl methacrylate (MMA) to prepare the graft copolymers (19–50 mol% of TMAMA units) serving as the drug (co)delivery systems. The in vitro drug release, which was driven by the exchange reaction of the pharmaceutical anions to phosphate ones in PBS medium, was observed for 44% of CLX¯ (2.7 μg/mL) and 53% of FUS¯ (3.6 μg/mL) in the single systems. Similar amounts of released drugs were detected for the dual system, i.e., 41% of CLX¯ (2.2 μg/mL) and 33% of FUS¯ (2.0 μg/mL). The investigated drug ionic polymer conjugates were examined for their cytotoxicity by MTT test, showing a low toxic effect against human bronchial epithelial cells (BEAS-2B) and normal human dermal fibroblasts (NHDF) as the normal cell lines. The satisfactory drug contents and the release profiles attained for the well-defined graft polymers with ionically bonded pharmaceuticals in the side chains make them promising drug carriers in both separate and combined drug delivery systems.

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

“…Therefore, advanced functional copolymers, e.g. drug delivery carriers, with various topologies ranging from linear, star-shape to grafted, have been synthesized 29 – 33 . The presence of hydroxyl groups in the p(HEMA- co -MMA) also gives an opportunity for the introduction of the azo compound via the Mitsunobu reaction, which has already been used to modify polyesterimides 17 .…”

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.…”

Characterization of Graft Copolymers Synthesized from p-Aminosalicylate Functionalized Monomeric Choline Ionic Liquid

“…Their biocompatibility has been utilized in medical applications [10,[29][30][31], but, in the case of such polymerizable ILs, the polymeric conjugates have been attained [14]. So far, using this strategy, PILs with various topologies bearing salicylate [32], fusidate and/or cloxacillin [33], and p-aminosalicylate (PAS) ions [34] have been successfully synthesized.…”