The large-scale use of glyphosate pesticides in food production has attracted attention due to environmental damage and toxicity risks. Several regulatory authorities have established safe limits or concentrations of these pesticides in water and various food products consumed daily. The irreversible inhibition of acetylcholinesterase (AChE) activity is one of the strategies used for pesticide detection. Herein, we found that lipopeptide sequences can act as biomimetic microenvironments of AChE, showing higher catalytic activities than natural enzymes in an aqueous solution, based on IC₅₀ values. These biomolecules contain in the hydrophilic part the amino acids L-proline (P), L-arginine (R), L-tryptophan (W), and L-glycine (G), covalently linked to a hydrophobic part formed by one or two long aliphatic chains. The obtained materials are referred to as compounds 1 and 2, respectively. According to fluorescence assays, 2 is more hydrophobic than 1. The circular dichroism (CD) data present a significant difference in the molar ellipticity values, likely related to distinct conformations assumed by the proline residue in the lipopeptide supramolecular structure in solution. The morphological aspect was further characterized using small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM), which showed that compounds 1 and 2 self-assembly into cylindrical and planar core–shell structures, respectively. The mimetic AchE behaviour of lipopeptides was confirmed by Ellman's hydrolysis reaction, where the proline residue in the peptides act as a nucleophilic scavenger of organophosphate pesticides. Moreover, the isothermal titration calorimetry (ITC) experiments revealed that host–guest interactions in both systems were dominated by enthalpically-driven thermodynamics. UV-vis kinetic experiments were performed to assess the inhibition of the lipopeptide catalytic activity and the IC₅₀ values were obtained, and we found that the detection limit correlated with the increase in hydrophobicity of the lipopeptides, implying the micellization process is more favorable.

The incorporation of drugs into nanostructured silica has proven to be an effective strategy for delaying drug release, protecting against enzymatic degradation, and enhancing therapeutic efficacy. Specifically, crotoxin, a component derived from the venom of Crotalus durissus terrificus, exhibits notable analgesic and immunomodulatory properties. Previous studies have demonstrated that encapsulating crotoxin within SBA-15 nanostructured mesoporous silica not only reduces its toxicity and enhances its analgesic effects but also enables effective oral administration. Given its promising efficacy and the expanding interest in its application across various experimental models and potential therapeutic uses, this study aimed to conduct a detailed analysis of the physicochemical properties of crotoxin when incorporated into SBA-15 silica. Following the characterization, the crotoxin–SBA-15 complex was orally administered in an experimental model of ulcerative colitis (UC) in mice. The most widely adopted experimental model for studying UC involves the administration of dextran sodium sulfate (DSS) in drinking water to induce colonic inflammation in susceptible animals. In this study, we hypothesized that crotoxin incorporated into ordered mesoporous silica (SBA-15) could modulate DSS-induced UC. Crotoxin was successfully incorporated into SBA-15 and administered orally, as its physicochemical properties supported this delivery approach. Mice received the crotoxin–SBA-15 complex either at the onset of UC induction or on days 1 and 4 after DSS exposure. Seven days after the start of DSS administration, we observed a substantial reduction (approximately 50%) in Disease Activity Index (DAI) scores, accompanied by marked improvements in the histopathological features of the colon. These findings indicate for the first time that crotoxin incorporated into SBA-15 exhibits significant therapeutic potential in the treatment of experimentally induced ulcerative colitis.