Bioactive linear poly(ionic liquid)s (PIL) were designed as carriers in drug delivery systems (DDS). Their synthesis was based on a monomeric ionic liquid (MIL) with a relevant pharmaceutical anion to create therapeutically functionalized monomers, which further can be used in the controlled atom transfer radical polymerization (ATRP). The presence of chloride counterions in the quaternary ammonium groups of choline MIL, e.g., [2-(methacryloyloxy)ethyl]trimethyl-ammonium chloride (ChMACl), was stimulated to undergo the anion exchange with p-aminosalicylate sodium salt (NaPAS) as the source of the pharmaceutical anion with antibacterial activity. The resultant [2-(methacryloyloxy)ethyl]trimethylammonium p-aminosalicylate (ChMAPAS) was copolymerized to attain the well-defined linear choline-based copolymers with various contents of PAS anions (24–42%), which were regulated by the initial ratio of ChMAPAS to MMA and conversion degree. The length of polymeric chains was evaluated by the total monomer conversion (31–66%) yielding degree of polymerization (DP_n = 133–272). Depending on the polymer carrier composition, PAS anions were exchanged by 60–100% within 1 h, 80–100% within 4 h, and completely after 24 h by phosphate anions in PBS imitating a physiological fluid.

Previously reported amphiphilic linear and graft copolymers, derived from the ionic liquid [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA_Cl‾), along with their conjugates obtained through modification either before or after polymerization with p-aminosalicylate anions (TMAMA_PAS‾), were employed as matrices in drug delivery systems (DDSs). Based on the counterion type in TMAMA units, they were categorized into single drug systems, manifesting as ionic polymers with chloride counterions and loaded isoniazid (ISO), and dual drug systems, featuring ISO loaded in self-assembled PAS conjugates. The amphiphilic nature of these copolymers was substantiated through the determination of the critical micelle concentration (CMC), revealing an increase in values post-ion exchange (from 0.011–0.063 mg/mL to 0.027–0.181 mg/mL). The self-assembling properties were favorable for ISO encapsulation, with drug loading content (DLC) ranging between 15 and 85% in both single and dual systems. In vitro studies indicated ISO release percentages between 16 and 61% and PAS release percentages between 20 and 98%. Basic cytotoxicity assessments using the 2,5-diphenyl-2H-tetrazolium bromide (MTT) test affirmed the non-toxicity of the studied systems toward human non-tumorigenic lung epithelial cell line (BEAS-2B) cell lines, particularly in the case of dual systems bearing both ISO and PAS simultaneously. These results confirmed the effectiveness of polymeric carriers in drug delivery, demonstrating their potential for co-delivery in combination therapy.

Bioactive linear choline-based copolymers were developed as micellar carriers for drug delivery systems (DDSs). The polymethacrylates containing trimethylammonium groups with p-aminosalicylate anions (PAS-based copolymers: series 1) or chloride anions (Cl-based copolymers: series 2) differing in ionic content and chain length were selected for drug loading. The diverse structures of amphiphilic copolymers made it possible to adjust the encapsulation efficiency of a well-known antibiotic, i.e., p-aminosalicylate in the form of sodium salt (PASNa) or acid (PASA), providing single drug systems. Goniometry was applied to verify the self-assembly capacity of the copolymers using the critical micelle concentration (CMC = 0.03–0.18 mg/mL) and the hydrophilicity level quantifying the surface wettability of polymer film using the water contact angle (WCA = 30–53°). Both parameters were regulated by the copolymer composition, indicating that the increase in ionic content caused higher CMC and lower WCA, but the latter was also modified to a less hydrophilic surface by drug encapsulation. The drug content (DC) in the PAS-based polymers was increased twice by encapsulation of PASNa and PASA (47–96% and 86–104%), whereas in the chloride-based polymer systems, the drug was loaded in 43–96% and 73–100%, respectively. Efficient drug release was detected for PASNa (80–100% series 1; 50–100% series 2) and PASA as complete in both series. The strategy of loading extra drug by encapsulation, which enhances the drug content in the copolymers containing anions of the same pharmaceutics, provided promising characteristics, which highlight the potential of PAS-loaded micellar copolymers for drug delivery.

Single and dual-drug delivery systems (DDSs) based on linear choline polymers were designed through the controlled polymerization of a pharmaceutically functionalized monomer, i.e., [2-(methacryloyloxy)ethyl]trimethylammonium, with counterions of cloxacillin (TMAMA/CLX), or its copolymerization with [2-(methacryloyloxy)ethyl]trimethylammonium with ampicillin (TMAMA/AMP), providing antibiotic properties. This strategy was effective in attaining well-defined linear copolymers with 38–93 mol. % of TMAMA content, which were regulated by the initial ratio of TMAMA to methyl methacrylate comonomer. The polymer compositions were controlled by the total monomer conversion (40–75%), resulting in a variable degree of polymerization (DP_n = 160–300) and pharmaceutical anion contents (CLX⁻ 51–80% and AMP⁻ 78–87%). In aqueous solution, the polymers formed particles with sizes ranging between 274 and 380 nm for CLX⁻ systems and 288–348 nm for CLX⁻/AMP⁻ systems. In vitro drug release, driven by the exchange of pharmaceutical anions with phosphate ions in phosphate-buffered saline (PBS), imitating a physiological fluid, demonstrated release efficiencies of 58–76% for CLX⁻ (10.5–13.6 µg/mL) in single systems, and 91–100% for CLX⁻ (12.9–15.1 µg/mL) and 97–100% for AMP⁻ (21.1–23.3 µg/mL) in dual systems. Compared to conventional systems delivering antibiotics without a polymer carrier, the choline-based polymer DDS attained satisfactory levels of drug loading content and (co-)release from the polymer carriers, offering a promising alternative for antibiotic delivery.