Linear Copolymers Based on Choline Ionic Liquid Carrying Anti-Tuberculosis Drugs: Influence of Anion Type on Physicochemical Properties and Drug Release

Abstract

In this study, drug nanocarriers were designed using linear copolymers with different contents of cholinium-based ionic liquid units, i.e., [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA/Cl: 25, 50, and 75 mol%). The amphiphilicity of the copolymers was evaluated on the basis of their critical micelle concentration (CMC = 0.055–0.079 mg/mL), and their hydrophilicities were determined by water contact angles (WCA = 17°–46°). The chloride anions in the polymer chain were involved in ionic exchange reactions to introduce pharmaceutical anions, i.e., p-aminosalicylate (PAS−), clavulanate (CLV−), piperacillin (PIP−), and fusidate (FUS−), which are established antibacterial agents for treating lung and respiratory diseases. The exchange reaction efficiency decreased in the following order: CLV− > PAS− > PIP− >> FUS−. The hydrophilicity of the ionic drug conjugates was slightly reduced, as indicated by the increased WCA values. The major fraction of particles with sizes ~20 nm was detected in systems with at least 50% TMAMA carrying PAS or PIP. The influence of the drug character and carrier structure was also observed in the kinetic profiles of the release processes driven by the exchange with phosphate anions (0.5–6.4 μg/mL). The obtained polymer-drug ionic conjugates (especially that with PAS) are promising carriers with potential medical applications.

Toxicity Evaluation of Choline Ionic Liquid-Based Nanocarriers of Pharmaceutical Agent For Lung Treatment With Extra Antitumor Activity

“…paminosalicylate (PAS), clavulanate (CLV) and piperacillin (PIP). The previous studies on physicochemical characterization, as well as the drug introduction, and release process have proved that the polymer obtained by ATRP at 40 C, where the ratio of TMAMA/MMA units was equal to 25/75, is a promising drug vehicle 37 . The polymer ability to self-organization was con rmed by critical micelle concentration (CMC = 0.055 mg/mL), whereas the formed nanoparticles including those with therapeutic counterions reached sizes ranging in 170290 nm.…”

“…Table 1 Characteristics of linear TMAMA copolymer (LC) and its conjugates with PAS, CLV, and PIP anions 37 LC: P(TMAMA-co-MMA) with the average molecular weight M n = 46900 g/mol, and dispersity index Ð = 1.74; DP n is the polymerization degree; F TMAMA is the content of TMAMA units; D h is hydrodynamic diameter by dynamic light scattering (DLS); WCA is water contact angle via goniometry using the sessile drop method; DC is drug content evaluated by UV-Vis.…”

“…adenocarcinoma human alveolar basal epithelial cells (A549) and human non-small cell lung carcinoma cell line (H1299), and normal one, namely human bronchial epithelial cells (BEAS-2B), of the ionic drugpolymer carrier. The previously synthesized well-de ned linear copolymers of (2-trimethylammonium)ethyl methacrylate and methyl methacrylate (LC) have been investigated successfully by their ability to self-assembling and anion exchange 37 . The biological activity of the ionic copolymers has been generated by the formation of its conjugates with antibacterial drugs in ionic form, i.e.…”

Research Progress on Typical Quaternary Ammonium Salt Polymers

“…Water-soluble polymers are a kind of strong hydrophilic macromolecule that can dissolve or swell in water to form aqueous solutions or dispensing systems. Because of the changeable features of their molecular weight, hydrophilic strength and quantity of feature function groups, water-soluble polymers are widely used in papermaking, water treatment, oil drilling, daily chemicals, and other traditional areas; they also play a key role in strategic emerging industries such as medicine, photovoltaics, artificial intelligence and new energy materials [1][2][3][4][5].…”

Biological In Vitro Evaluation of PIL Graft Conjugates: Cytotoxicity Characteristics

“…Numerous reports have been devoted to the use of phosphorylcholine IL as a co-monomer to obtain linear block copolymers [ 24 , 25 ], whereas those with graft topology and containing ionic units, i.e., imidazolium [ 26 ] or choline-type IL [ 12 , 27 ] in the side chains, have been investigated with significantly lower attention. In the case of the ionic polymer structure, drugs can be carried in ionic form as counterions, i.e., nicotinic, salicylic, ampicillin, naproxen, ibuprofenate anions [ 28 , 29 , 30 ], as well as in nonionic form as loaded guests [ 31 ], or both forms as the systems for combined therapy [ 32 ].…”