No abstract

Bacteria are constantly developing greater antibiotic resistance; therefore, safe, efficacious, and cost-effective antibiotics are urgently needed. Ionic liquids (ILs) show great promise as antimicrobial agents because of their ability to disrupt bacterial membranes. In this study, a library of choline carboxylic acid-based ionic liquids were synthesized and utilized in vitro to discern their antimicrobial activity against Escherichia coli and methicillinresistant Staphylococcus aureus (MRSA). Here, choline was combined with carboxylic acids of varying alkyl chain lengths, degrees of saturation, and mole ratios and then added to E. coli and MRSA at different concentrations to determine the minimal bactericidal concentration (MBC). The MBC is linked to the presence of the anion because, when the cation is held constant, increasing the alkyl chain to its peak length, doubling the mole ratio, and removing the π bonds with respect to the anion tend to decrease MBC values, illustrating greater killing efficacy. This investigation provides insight into how the identity of the anion impacts the biocompatibility of the IL and the growth inhibition and morphology of the bacteria, ultimately establishing this class of materials as an effective, human-safe, and low-cost option for eradication of Gram-positive and Gram-negative bacteria.

Ionic liquids (ILs) have been shown to be effective transdermal penetrants of pharmaceutically active ingredients, including small molecules and proteins. The presence of water within ionic liquids has been demonstrated to play a critical role in  their structural organization on the molecular level. However, the impact of water on IL transdermal transport efficacy has yet to be investigated. Herein, a water concentration gradient (0%–100% v/v) is tested to evaluate  choline trans‐2‐octenoic (CA2OE)‐mediated transport of a hydrophilic model drug dextran (10000 Da) in an ex vivo porcine skin model.Compared to 2:1, 1:1, 1:4, and 1:5 ionic ratio formulations, 50% v/v CA2OE 1:2‐water evidences the greatest success at transporting dextran to the acceptor fluid. Physicochemical characterization (dynamic light scattering (DLS), scanning electron microscopy (SEM), optical density (O.D.), Fourier transform infrared spectroscopy (FTIR), fluorescent microscopy, and rheology) is conducted to test both bulk and nanoscale‐level CA2OE 1:2–water interactions. It is hypothesized that the presence of microemulsions in the CA2OE 1:2 75% v/v formulation accounted for the severely decreased transport compared to the 50%. It is thus critical to comprehensively consider interactions between IL components, co‐solvents, anddrug molecules when formulating ILs for transdermal transport applications.

At 50% (v/v) water composition, the ionic liquid (IL) choline trans‐2‐octenoic acid (CA2OE 1:2) forms a lamellar‐organized nanoparticle (cross‐section) encapsulating fluorescent rhodamine‐dextran (pink), which allows for deep penetration through the epidermal layer of porcine skin (pink; right) to the dermis and access its vascular network (below; nerves (red and blue), blood vessels (dark red), and adipocytes (yellow)) during transdermal delivery This is reported by Eden E. L. Tanner and co‐workers in article number 2200096.

Less than 5% of intravenously-injected nanoparticles (NPs) reach destined sites in the body due to opsonization and immune-based clearance in vascular circulation. By hitchhiking in situ onto specific blood components post-injection, NPs can selectively target tissue sites for unprecedentedly high drug delivery rates. Choline carboxylate ionic liquids (ILs) are biocompatible liquid salts <100℃ composed of bulky asymmetric cations and anions. This class of ILs has been previously shown to significantly extend circulation time and redirect biodistribution in BALB/c mice post-IV injection via hitchhiking on red blood cell (RBC) membranes. Herein, we synthesized & screened 60 choline carboxylic acid-based ILs to coat PLGA NPs and present the impact of structurally engineering the coordinated anion identity to selectively interface and hitchhike lymphocytes, monocytes, granulocytes, platelets, and RBCs in whole mouse blood for in situ targeted drug delivery. Furthermore, we find this nanoparticle platform to be biocompatible (non-cytotoxic), translate to human whole blood by resisting serum uptake and maintaining modest hitchhiking, and also significantly extend circulation retention over 24 hours in BALB/c healthy adult mice after IV injection. Because of their altered circulation profiles, we additionally observe dramatically different organ accumulation profiles compared to bare PLGA NPs. This study establishes an initial breakthrough platform for a modular and transformative targeting technology to hitchhike onto blood components with high efficacy and safety in the bloodstream post-IV administration.