Mucus is a viscoelastic gel that acts as a protective barrier for epithelial surfaces. The mucosal vehicles and adjuvants need to pass through the mucus layer to make drugs and vaccine delivery by mucosal routes possible. The mucoadhesion of polymer particle adjuvants significantly increases the contact time between vaccine formulations and the mucosa; then, the particles can penetrate the mucus layer and epithelium to reach mucosa-associated lymphoid tissues. This review presents the key findings that have aided in understanding mucoadhesion and mucopenetration while exploring the influence of physicochemical characteristics on mucus–polymer interactions. We describe polymer-based particles designed with mucoadhesive or mucopenetrating properties and discuss the impact of mucoadhesive polymers on local and systemic immune responses after mucosal immunization. In future research, more attention paid to the design and development of mucosal adjuvants could lead to more effective vaccines.

Although chlorogenic acid, suramin, ursolic acid, and the glycyrrhetinic acid derivative FC122 are individually known PTP1B inhibitors, no study has systematically characterized how mechanistic diversity determines the pharmacological outcome of their combinations. Here, we integrate experimental enzyme kinetics, molecular docking, molecular dynamics (MD), and membrane permeability simulations to address this question. Individual inhibitory potencies ranked SUR > FC122 > UA > CGA (IC ₅₀ : 1.82, 3.27, 6.12, and 252 µM, respectively). Fixed‐ratio combination experiments showed two distinct profiles: additivity for the uncompetitive + mixed pair (FC122 + UA) and competitive + competitive pairs (SUR + CGA), and antagonism for the competitive + uncompetitive combination (SUR + FC122). Docking and MD provided the structural basis for these results and suggested that each combination imposes a distinct structural flexibility profile on the disordered C‐terminal region of PTP1B (residues 300–400). For the first time, the MD‐AMBER‐Umbrella‐COM protocol was applied to generate a comparative membrane permeability profile for mechanistically diverse PTP1B inhibitors, proposing a permeability order (SUR > FC122 > CGA ≈ UA). These results suggest that kinetic compatibility is a more reliable predictor of promising inhibitor combinations than binding‐site geography alone, and they offer a rational framework for designing multisite PTP1B inhibition strategies in type 2 diabetes mellitus.

Selective PTP1B inhibitors paradoxically potentiate oncogenic STAT3 signaling by restoring JAK2 activity, underscoring the need for dual-target strategies. Here we report that BP-1-102, an orally bioavailable STAT3 SH2 domain inhibitor, also potently inhibits PTP1B with IC₅₀ values of 5.32 μM (hPTP1B_1–400) and 11.7 μM (hPTP1B_1–285), with ≥37.7-fold selectivity over TCPTP. Kinetic analysis identified an uncompetitive mechanism, suggesting inhibitor binding to the enzyme–substrate complex at a site distal to the active site. Docking and 500 ns molecular dynamics simulations revealed a dual-anchor binding mode involving the 113–123 loop (Cys121) and the proline-rich C-terminal disordered region, a structural interface absent in TCPTP. Umbrella sampling confirmed favorable passive membrane permeability through a tumor-mimetic bilayer (ΔG = −13.83 kcal/mol). These results propose BP-1-102 as a candidate for dual-function inhibitor of the PTP1B–JAK2–STAT3 oncogenic axis, providing a physicochemical and mechanistic rationale for its further evaluation in tumors where both targets are coactivated.

Periplasmic binding proteins (PBPs) are attractive scaffolds for fluorescent biosensors because they undergo large ligand-induced conformational changes and exhibit high specificity. Despite their potential, generalizable design strategies have been hindered by an incomplete understanding of how labeling positions influence protein dynamics and signal transduction. Here, we established a systematic experimental framework using the lysine-arginine-ornithine binding protein (LAO) as a model to characterize PBP-based fluorescent biosensors. Seven positions classified as endosteric, peristeric, or allosteric relative to the binding site were labeled with monobromobimane (mBBr). Our characterization revealed position-dependent effects on quantum yields, fluorescence intensity changes, ligand-binding affinities, and thermal stability. Molecular dynamics simulations (MD) of wild-type and mBBr-labeled variants provided a mechanistic context for these experimental observations. Functional biosensor positions (D51C, D53C, K228C, Y230C, and E167C) maintained open-like conformations necessary for signal generation upon ligand encounter. In contrast, peristeric position A89C, located at the hinge region, spontaneously adopted a closed-like conformation even in the absence of ligand, resulting in an inverse fluorescence response and reduced affinity. These results demonstrate that while structural criteria can guide initial site selection, experimental validation remains essential, as static structures alone cannot predict the complex interactions among labeling position, dynamics, and biosensor function. The experimental and computational framework established here with LAO as a model system provides methodological principles that may inform biosensor engineering from other PBP scaffolds, while emphasizing that conformational dynamics must be considered alongside static structural criteria.

Vaginal drug delivery offers a critical route for local treatments but is limited by short formulation residence times. This study describes a thermosensitive in situ gel prepared by the cold-dissolution method from a ternary blend of Pluronic F127, Carbopol 940, and HPMC for localized vaginal therapy. We used ibuprofen as a model drug selected for its reported anti-inflammatory and antiproliferative activity. The hydrogels exhibited a constant gelation temperature of 28 °C and high viscosity under simulated physiological conditions; ibuprofen incorporation further reduced susceptibility to gravitational leakage. FTIR, XRD, and DSC analyses confirmed stable physical cross-linking of the polymer network and amorphous molecular dispersion of ibuprofen. Peppas–Sahlin modelling revealed a controlled, sustained release profile (>50% over 24 h) predominantly governed by Fickian diffusion (69%). The blank hydrogel exhibited high biocompatibility (>75% viability). In contrast, the ibuprofen-loaded matrix exhibited a concentration-dependent cytotoxic effect on HeLa cervical cancer cells, reducing cell viability to ~12% at the full extract concentration. Overall, this ternary hydrogel platform represents a stable, promising vehicle for sustained local administration of ibuprofen in the vaginal microenvironment.