Antimicrobial resistance is a current critical challenge, requiring the urgent development of new, effective broad-spectrum antimicrobials. To tackle this challenge, in this work, naturally occurring B vitamins, viz. nicotinamide, nicotinic acid and p-aminobenzoic acid, were used as precursors of both the cation and anion to design novel ionic liquids (ILs) in the form of quaternary ammonium salts (QASs). These combinations allowed for the development of multifunctional (anti-inflammatory and antimicrobial) agents targeting oral administration. The QASs were synthesized, characterized, and evaluated for the therapeutic potential as well as mechanism of the antimicrobial activity. Mixtures and cocrystals of the starting materials were also investigated for comparison purposes. Salts with the p-aminobenzoate anion showed excellent anti-inflammatory activity, inhibiting albumin denaturation by up to 54%, remarkably outperforming diclofenac sodium at its peak plasma concentration. Both albumin-based and in silico COX-2 studies further indicated that increasing the alkyl chain length significantly enhances the compounds’ efficacy. Antimicrobial tests showed that QASs were up to 250 times more effective than their non-ionic analogues. Moreover, the salts with the highest bactericidal activity completely inhibited biofilm growth against S. aureus and P. aeruginosa. Solubility studies under simulated gastrointestinal pH showed higher solubility of QASs, up to 100-fold, compared to the non-ionic forms. Cytotoxicity assay using human normal small intestinal cells (HIEC-6) revealed that even the most potent vitamin B analogues, were approximately ten times less toxic than the widely applied pharmaceutical agent, benzalkonium chloride. Ecotoxicity studies using A. franciscana also confirmed their low environmental impact.
Nicotine replacement therapy (NRT) remains one of the most widely used strategies for smoking cessation. However, currently available products are limited by fixed-dose strengths and poor adaptability to release behavior. In this study, an inkjet-printed nicotine buccal film platform was developed to enable quantitative dose control and folding-dependent modulation of drug release. Five aqueous nicotine inks were prepared to evaluate printability. Nicotine deposition showed strong correlations with print number, printed area, and calculated Z value, confirming predictable and digitally controllable drug loading. Among the tested substrates, the polyethylene oxide (PEO)-based ML8 formulation showed the sharpest printed boundary and the highest elongation at break and was selected as optimal. In the ML8 system, the casting thickness influenced the mechanical flexibility and early stage drug release without compromising the printing quality or adhesive behavior. Physicochemical analyses using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR) showed that nicotine remained chemically and thermally stable after printing, whereas the intrinsic semi-crystalline structure of the PEO-rich substrate was preserved. Notably, drug release from the ML8 films could be modulated by the folding configuration alone, without altering the formulation composition. Increasing the number of folds progressively slowed the drug release and reduced the Korsmeyer–Peppas release rate constant, revealing that folding can serve as a practical structural parameter for release control. Overall, this study established inkjet-printed nicotine buccal films as a digitally fabricated platform in which the dose is controlled by printing parameters and the release is tuned by structural design.
