Trimethylammonium-Based Polymethacrylate Ionic Liquids with Tunable Hydrophilicity and Charge Distribution as Carriers of Salicylate Anions

Abstract

Copolymers of [2-(methacryloyloxy)ethyl]trimethylammonium chloride, salicylate or bis(trifluoromethanesulfonate)imide (Cl − , Sal − or Tf 2 N − ), and methyl methacrylate (MMA) were synthesized by atom transfer radical polymerization (ATRP). The effect of different molar fractions of ionic monomer (0.05−1.0) on physicochemical properties was investigated. The relative reactivity ratios of MMA and ionic monomer with the chloride anion (0.88 and 1.13, respectively) were determined by the linearization Jaacks method. The particles formed in water by copolymers with trimethylammonium chloride (≥50 mol %) reached sizes below 10 nm, whereas salicylate-containing copolymers supported strong self-assembly, yielding 200 nm superstructures. The copolymers, after modification by the exchange of Cl − and Sal − with Tf 2 N − , demonstrated the influence of the anion on solubility, glass transition temperature, and morphology. The anionmodified trimethylammonium copolymers, compared with those directly synthesized from Tf 2 N-containing monomer, indicated different properties. Both the chloride monomer (Cl − replaced by Sal − or Tf 2 N − ) and its copolymers are able to exchange anions, including biologically active ones, which extends their future applications as poly(ionic liquid)s with therapeutic properties for controlled drug delivery.

Synthesis and Characterization of Ionic Graft Copolymers: Introduction and In Vitro Release of Antibacterial Drug by Anion Exchange

“…This molecule supports biological functions [ 34 , 37 , 38 ] as a precursor of acetylcholine [ 39 ]. The presence of an ionic group in the cholinium unit gives the opportunity for the ion exchange reaction, which in the case of polymerized ionic liquids can be advantageous for incorporation of pharmaceutical ions, i.e., sulfacetamid, salicylate [ 40 , 41 , 42 ]. There are also reports of other types of PILs, based on imidazolium and pyridinium transporting naproxen anions [ 43 ] or guanidinium with ampicillin anions [ 44 ].…”

Ionic Polymethacrylate Based Delivery Systems: Effect of Carrier Topology and Drug Loading

“…They gained great interest in material science because of macromolecular architectures, which can be tailored by combining both properties of cations and anions [38]. In our recent studies on the amphiphilic graft copolymers, the monomeric ionic liquids, i.e., commercially available (2-(methacryloyloxy)ethyl)-trimethylammonium chloride (ChMACl known as choline methacrylate) and containing pharmaceutical salicylate anion (ChMASal, [39,40]), were grafted from the standard multifunctional ATRP macroinitiators, i.e., poly(methyl methacrylate- co -(2-(2-bromoisobutyryloxy)ethyl methacrylate))) (poly(MMA- co -BIEM: MI) [41,42] with various contents of bromoester initiating groups, 25–75% (GPIL1 series and GPIL2, Figure 1c, Table 1). The side chains resulted in the use of methyl methacrylate (MMA) as the comonomer.…”

“…For comparison, the analogous linear poly(ionic liquid)s (LPIL1–2) were synthesized using standard ATRP initiator. i.e., ethyl α-bromoisobutyrate (EBiB) [39,40]. The LPIL systems, both chloride (LPIL2.1) and salicylate (LPIL1.1–1.2) ones in relation to analogical GPIL, exhibited higher drug loading content (DLC LPIL > DLC GPIL ), but this difference was significantly higher for salicylate systems, whereas the opposite DLC dependency was indicated for IMC encapsulation [44].…”

Salicylate Poisoning Potential of Topical Pain Relief Agents: From Age Old Remedies to Engineered Smart Patches

“…There remains considerable research into the design of supramolecular gelation layers than can encapsulate salicylates—and MS, in particular, with the aim of enhancing the biocompatibility of the host matrix and enabling more controllable release of the therapeutic agent [ 62 , 63 , 64 ]. While there are numerous formulations available, it is important to note that very few have been approved by the FDA for the temporary relief of pain relative to the many conditions associated with chronic pain, as indicated in Table 2 .…”