Search Results (295)

Mucoadhesive drug delivery systems have emerged as a promising strategy to enhance the therapeutic efficacy of pharmaceuticals by improving drug residence time, bioavailability, and site-specific targeting. Among various materials investigated, biopolysaccharides have gained significant attention due to their biocompatibility, biodegradability, non-toxicity, and inherent mucoadhesive properties. Natural polymers such as chitosan, alginate, pectin, hyaluronic acid, and cellulose derivatives exhibit strong interactions with mucosal surfaces through hydrogen bonding, electrostatic interactions, and polymer chain entanglement. These properties enable prolonged drug retention at mucosal sites, controlled drug release, and enhanced permeation across biological barriers. Mucoadhesive biopolysaccharides have been explored for diverse routes of administration, including oral, buccal, nasal, ocular, vaginal, and pulmonary delivery. Furthermore, chemical modification and nanostructuring of these polymers have expanded their functionality, enabling targeted delivery of small molecules, proteins, peptides, and nucleic acids. This review highlights the mechanisms of mucoadhesion, key biopolysaccharides used in drug delivery, formulation approaches, and recent advances in their application as versatile platforms for novel therapeutic delivery systems. The continued development of mucoadhesive biopolysaccharide-based carriers holds substantial potential for improving treatment outcomes and patient compliance. Full article

Inflammatory bowel disease (IBD) is a chronic relapsing disorder associated with dysregulated interactions among the gut microbiota, mucosal immunity, and the intestinal barrier. Although current treatments have improved disease control, incomplete response, adverse effects, and relapse remain common. Berberine, a natural isoquinoline alkaloid, has gained attention as a multitarget compound with potential relevance to IBD. This narrative review summarizes evidence published up to March 2026 on the pharmacological basis, delivery optimization, clinical translation, and microbiota–immune–barrier axis regulation of berberine in IBD. Current evidence suggests that berberine may reshape gut microbial communities, regulate mucosal immune responses, and support epithelial barrier repair, thereby contributing to the restoration of intestinal homeostasis. Emerging formulation strategies, particularly microbiota-responsive and intestine-targeted delivery systems, may improve local exposure and strengthen its therapeutic potential. However, the current evidence is still dominated by preclinical studies. Clinical data remain limited, and the causal links among microbial remodeling, immune modulation, and barrier restoration are not yet fully defined. Future work should prioritize mechanistic validation, clinically relevant delivery design, and well-controlled clinical trials to clarify the role of berberine in personalized IBD management. Full article

Hydrogel scaffolds have emerged as instructive microenvironments for craniofacial tissue regeneration, moving beyond passive cell carriers toward platforms that regulate cell fate, vascularization, immune remodeling, and tissue-specific architecture. This review synthesizes hydrogel-associated strategies across dental pulp, periodontal ligament, gingival, bone marrow, jawbone, endothelial, oral mucosal, induced pluripotent stem cell (iPSC), extracellular vesicle (EV), exosome, secretome, and acellular systems. The evidence indicates that craniofacial hydrogel performance is governed by reciprocal interactions among biological source, scaffold composition, matrix mechanics, spatial architecture, mineral or ionic signaling, growth factor delivery, vesicle-mediated communication, and inflammatory niche modulation. Mineralized and ion-releasing hydrogels most consistently supported osteogenesis and bone repair, whereas extracellular matrix (ECM)-mimetic, peptide, collagen, fibrin, gelatin methacryloyl (GelMA), alginate, hyaluronic acid (HA), and chitosan-based systems enabled pulp–dentin, periodontal, peri-implant, oral mucosal, and soft-tissue reconstruction. Responsive, antimicrobial, antioxidant, conductive, and immunomodulatory hydrogels further expanded the field by targeting diseased microenvironments rather than regeneration alone. Despite strong preclinical evidence, translation remains limited by heterogeneity in scaffold formulations, biological sources, analytical endpoints, defect models, and long-term functional validation. Future progress will require standardized characterization, tissue-specific design criteria, clinically relevant large-animal models, scalable cell-free technologies, and integrated assessment of regeneration, immunity, vascularization, innervation, mechanics, and safety. Full article

In ulcerative colitis (UC), the therapeutic efficacy of nanoparticle (NP)-based drug delivery systems is limited by premature drug release, uptake or degradation of NPs during their passage through the harsh gastrointestinal tract (GIT) environment, poor colon targeting, and rapid NP clearance caused by diarrhea symptoms. This study focused on designing an advanced spatiotemporally controlled nanohybrid hydrogel drug delivery system to overcome these challenges. We developed a pH- and temperature-responsive polysaccharide-based hydrogel composed of chitosan (CS), β-glycerol phosphate disodium salt pentahydrate (GP), hydroxypropyl cellulose (HPC), and collagen type I (Col I), designated as CS/HHPC/Col I-GP. The hydrogel exhibited a dense and uniform porous reticular structure, with an average pore diameter of 127.45 ± 2.22 μm. The equilibrium swelling ratio of the CS/HHPC/Col I-GP was determined to be 32.10 ± 1.11 g/g, indicating excellent swelling capacity and sustained structural stability over 6 h—making it suitable for sustained drug release in the intestinal tract. Then, the prepared curcumin nanoparticles (CurNPs) were encapsulated into the CS/HHPC/Col I-GP hydrogel to form the CS/HHPC/Col I-GP-CurNPs composite. The polysaccharide-based hydrogel shell of the formulation withstood harsh gastrointestinal conditions, enabled targeted adhesion to the colon, and was specifically degraded by colonic enzymes. The CurNPs released in the colon benefit from their negatively charged characteristics, enabling accumulation at the positively charged inflamed sites and achieving sustained Cur release. The results of the gastrointestinal digestion simulation experiment showed that the cumulative release of CS/HHPC/Col I-GP-CurNPs was only 12.33 ± 2.17% in simulated gastric fluid (SGF) and reached 96.91 ± 1.98% in simulated colonic fluid (SCF) after 60 h. Cell and animal experimental data confirmed that the formulation significantly alleviated colitis symptoms by modulating the repolarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 phenotypes and deactivating the TLR4/MyD88/NF-κB pathway. Furthermore, the integrity of the intestinal mucosal barrier and the gut microbiota were enhanced. This study provides a promising strategy for the oral drug treatment of UC. Full article

Background: Paranasal sinuses and mastoid air cells have been attributed to multiple functions—such as voice resonance, cranial lightening, and pressure regulation—yet their potential role in local thermal homeostasis remains underappreciated. The thermoregulatory hypothesis, first proposed in the mid-twentieth century, was largely abandoned after the mid-century, when anthropological findings of climate-correlated variation seemed contradictory. Hypothesis: We propose that pneumatized skull regions form a three-component craniofacial biothermal system that maintains thermal stability in the ocular vitreous and vestibular endolymph, two avascular, temperature-sensitive structures that lack intrinsic thermoregulatory capacity. This represents a novel integration that explicitly links paranasal and mastoid pneumatization into a coordinated system that protects sensory organs, distinct from previous brain-cooling hypotheses. Mechanism: The system comprises: (1) passive thermal insulation via air spaces, providing ~15-fold greater thermal resistance than bone; (2) active cold protection via mucosal heat delivery (estimated 2–5 W capacity); and (3) active heat dissipation via evaporative cooling (estimated 0.3–0.5 W capacity). This architecture provides asymmetric protection, with cold buffering exceeding heat dissipation by approximately 5- to 15-fold, consistent with thermodynamic constraints and putative evolutionary priorities. Evidence: Preliminary observations consistent with this hypothesis include the anatomical proximity of pneumatized regions to the vitreous and labyrinth, intranasal selective brain cooling studies, and clinical observations after mastoidectomy showing preserved pressure buffering but reduced vestibular thermal insulation under extreme stimulation. Climate-correlated pneumatization patterns are consistent with bidirectional thermal adaptation. Implications: We present five falsifiable predictions that can be tested with thermographic imaging, pharmacological manipulation, and computational modeling. Validation could inform surgical planning, explain postoperative thermal-sensitivity symptoms, and provide evolutionary insights into craniofacial adaptation. Full article

Background: Avian influenza is a critical zoonotic infection threatening both the poultry industry and global public health. While traditional intramuscular vaccines elicit systemic immunity, they often fail to provide robust local protection at mucosal surfaces. There is thus significant interest in the development of mucosal avian influenza vaccines administered via the intranasal route. However, in humans, this approach is significantly hampered by the availability of safe and effective adjuvants. Methods: This study investigated the immunogenicity of a modified recombinant influenza A/H5 hemagglutinin (rHA/H5-modif) formulated with Novochizol, a novel chitosan-derived delivery system, administered intranasally to laboratory animals. Results: Our results demonstrate that mucosal immunization with the rHA/H5-modif/Novochizol complex induces potent humoral (IgG and IgA) and cell-mediated immune responses. Crucially, the formulation provided 100% survival in mice following a lethal challenge with highly pathogenic avian influenza A/H5. Conclusions: These findings position the rHA/H5-modif/Novochizol complex as a promising candidate for next-generation mucosal vaccines, in particular against highly pathogenic avian influenza A/H5 subtype. Full article

Cannabidiol (CBD), a major non-psychoactive phytocannabinoid, has attracted considerable attention owing to its broad therapeutic potential. Its anti-inflammatory, antimicrobial, and antitumor properties make it a promising candidate for the treatment of mucosa-associated diseases. However, the clinical translation of CBD is significantly hindered by its unfavorable physicochemical properties, particularly high lipophilicity and poor aqueous solubility, which result in low bioavailability. To overcome these limitations, the rational selection of administration routes in combination with advanced drug delivery systems tailored to disease pathophysiology is essential. Such strategies are critical for improving the stability of CBD, enhancing mucosal permeation, and enabling controlled and targeted release at diseased sites. Nevertheless, a systematic review focusing on these aspects is still lacking. This review first summarizes the relationship between CBD and the mucosal endocannabinoid system, together with its pharmacological effects. It then discusses the therapeutic potential of CBD in mucosal disorders of the digestive and respiratory systems. In addition, current administration routes and advanced delivery systems for CBD are reviewed to provide insights for future research and clinical translation. Finally, the remaining challenges associated with the clinical application of CBD and future development directions are discussed. Full article

Next-generation vaccines are being developed to elicit durable and cross-protective immune responses against diverse pathogens, particularly those targeting the respiratory and enteric systems. By strategically engaging T cell-centric antigen design, mucosal immune engagement, and induction of trained innate immunity, these innovative platforms are expected to reshape the paradigm of immunoprophylaxis and to offer promising avenues for enhanced protection against complex infectious diseases. Conventional antibody-based vaccines, though effective against many infections, often lack the capacity to induce durable or cross-protective immunity at mucosal surfaces. Advances in antigen design, delivery platforms, and adjuvant technologies now facilitate precise activation of tissue-resident memory T cells and enhancement of mucosal secretory IgA responses, thereby achieving sterilizing immunity at barrier surfaces while reinforcing systemic immune protection. Advanced delivery platforms, including lipid nanoparticles, viral vectors, and nano or liposomal carriers, further refine antigen presentation, enhancing stability, targeting, and overall immunogenicity. Concurrently, progress in understanding trained innate immunity highlights opportunities to induce broad, non-antigen-specific protection through epigenetic and metabolic reprogramming of innate cells. The integration of these adaptive and innate mechanisms may enhance early pathogen control, limits transmission, and strengthens defense against variant and antimicrobial-resistant pathogens across diverse populations. However, translating these immunological insights into safe, scalable, and globally accessible vaccines remains a major challenge. This review explores the emerging conceptual framework of next-generation vaccines that demonstrate partial integration of these axes in preclinical models, though human translation and functional synergy require Phase II validation. It highlights progress toward next-generation vaccines leveraging integrated adaptive and innate immune reprogramming for superior protection against respiratory and enteric pathogens. Full article

Background/Objectives: With the ongoing efforts in supporting the discovery of novel targeted drug delivery systems for the upper region of the female reproductive tract (FRT), it is imperative to understand the local drug disposition pathways. We aim to obtain a comprehensive profile of the drug transporters and drug-metabolizing enzymes in the human ectocervix, uterus, and fallopian tubes, as these factors may substantially influence mucosal penetration, tissue exposure, drug disposition, and the risk of drug–drug interactions. Methods: Gene expression of 12 drug transporters and 21 drug-metabolizing enzymes was quantified using RT-qPCR. Protein expression of highly expressed transporters was assessed using immunohistochemistry (IHC). Results: Among the 12 transporters analyzed, the efflux transporters P-gp, BCRP, and MRP4 exhibited the highest expression across the ectocervix, endometrium, myometrium, and fallopian tubes, with P-gp consistently showing the greatest abundance in all evaluated FRT tissues. Expression of these transporters was significantly higher (6–17×) in myometrium compared with ectocervix. IHC demonstrated strong localization of P-gp, BCRP, and MRP4 to epithelial layers facing the lumen, as well as to stromal and vascular endothelial cells. For drug-metabolizing enzymes, all 21 phase I and II enzymes were detectable across the FRT, and 15 were expressed at comparatively higher levels across all tissue types. These included CYP1A1, CYP1B1, CYP2B6, CYP2C8, CYP2C19, CYP3A4, UGT1A1, UGT1A3, UGT1A4, UGT1A7, UGT1A8, UGT1A10, UGT2B4, UGT2B15, and UGT2B17. Conclusions: The gene expression and localization data obtained from this work may improve our understanding of drug disposition in the FRT, which will inform selection, design, and optimization of drugs intended for targeted delivery within the FRT. Full article

Highly pathogenic avian influenza A (H7N9) remains a threat to poultry health and poses a zoonotic risk, highlighting the need for vaccine antigens capable of inducing both systemic and mucosal immunity. In this study, we evaluated X33CLS-H7, a clarified cell-lysate supernatant derived from glycoengineered Pichia pastoris expressing H7 hemagglutinin, in BALB/c mice following intramuscular(i.m.) injection, nebulized inhalation, or intranasal instillation. H7 expression and hemagglutination activity were confirmed by Western blotting and hemagglutination assay, respectively. Serum HA7-specific IgG and IgA responses, hemagglutination inhibition(HI) activity, H7N9 pseudovirus neutralization, bronchoalveolar lavage fluid (BALF) antibodies, and safety readouts were assessed. After two i.m. immunizations, X33CLS-H7 induced the strongest systemic antibody responses, with an HI geometric mean titer of 1:1622 95% CI, 1:1108–1:2348 and a mean log10 NT₅₀ of 4.62. Respiratory immunization also elicited antibody responses. After four doses, high-dose nebulized delivery produced the strongest responses among the respiratory delivery regimens, with serum IgG and IgA titers of 1.02 × 10⁵ and 2.24 × 10³, respectively, an endpoint HI GMT r of 1:457 95% CI, 1:211–1:971, and a mean log10 NT₅₀ of 3.77 compared with 2.02 in saline controls. High-dose nebulized delivery also generated detectable HA7-specific IgG and IgA responses in bronchoalveolar lavage fluid. No overt local or systemic toxicity signals were observed under the tested conditions. These findings indicate that X33CLS-H7 retains HA7-associated antigenicity and can induce systemic and respiratory mucosal antibody responses, supporting its further evaluation as a simplified and scalable H7N9 vaccine antigen candidate. Full article

Hydration, interfacial interactions, and matrix stability are critical determinants of the mucoadhesive behavior of cellulose-based polymers. In this study, we investigated the physicochemical and mucoadhesive behavior of hydroxypropyl methylcellulose (HPMC), Carbopol 974P NF, and Kollidon VA 64, along with their binary blends (1:1, w/w) in the context of oral mucosal drug delivery. Wettability, surface free energy, mucoadhesion, and hydration-induced morphological changes were systematically evaluated using contact angle measurements, adhesion and water uptake studies, and real-time surface dissolution imaging (SDi2). The investigated systems displayed markedly different water contact angles: HPMC 103.4 ± 2.7°, Carbopol 47.2 ± 2.3°, Kollidon 36.0 ± 1.8°, HPMC:Carbopol 51.3 ± 2.8°, and HPMC:Kollidon 53.9 ± 3.4°. The corresponding surface free energy (SFE) values ranged from 12.0 mJ/m² for HPMC to 70.5 mJ/m² for Kollidon. Experiments were performed under saliva-mimicking conditions containing 0.1% (w/v) mucin. The HPMC:Carbopol blend exhibited superior mucoadhesive performance and mechanical stability compared with HPMC alone or with the HPMC:Kollidon blends. In 2% (w/v) mucin, the HPMC:Carbopol blend reached a mucoadhesive force of approximately 1.35 N, whereas HPMC and HPMC:Kollidon showed lower values of approximately 0.5–0.75 N and 0.60 N, respectively. After 96 h at 85% RH, the swelling index increased from 14.8 ± 0.5% for HPMC to 29.4 ± 0.3% for HPMC:Carbopol. The incorporation of Carbopol increased the polar contribution to the surface free energy of HPMC-based blends and promoted stable gel layer formation, whereas Kollidon-containing systems underwent rapid disintegration and asymmetric deformation. SDi2 imaging showed that the HPMC disk changed proportionally by approximately 18% in both height and width during 12 h, whereas the HPMC:Kollidon disk almost completely dissolved after approximately 6 h. These results demonstrate that rational selection and combination of cellulose-based polymers can be used to control hydration, interfacial properties, and mucoadhesion, with HPMC:Carbopol blends showing strong potential for oral mucosal drug delivery. Full article

Bacterial membrane vesicles (BMVs), encompassing outer membrane vesicles (OMVs) released from Gram-negative bacteria and extracellular vesicles (EVs) released from Gram-positive bacteria, have emerged as promising vaccine platforms owing to their intrinsic immunostimulatory properties and capacity to deliver a wide range of antigens. Although conventional vaccines effectively prevent infectious diseases, their long-term efficacy is often limited by antigenic variation and reliance on a restricted number of licensed adjuvants. BMVs, as self-adjuvanting systems, enable both antigen delivery and innate immune activation. BMVs are nanoscale lipid bilayer structures enriched with pathogen-associated molecular patterns (PAMPs), facilitating their recognition and uptake by antigen-presenting cells. This leads to the activation of pattern recognition receptors and the induction of pro-inflammatory cytokines, type I interferons, and adaptive immune responses, including antibody production and Th1- and Th17-biased cellular immunity. Recent studies highlight the versatility of BMVs as vaccine platforms across bacterial, fungal, and viral infection models. BMVs induce protective immunity by promoting both systemic and mucosal immune responses, thereby reducing bacterial burden and limiting pathogen colonization across diverse infection models. These properties have supported their application in viral vaccine development, including influenza and SARS-CoV-2, with the potential to enhance mucosal immunity. Despite these advantages, challenges remain in standardization, safety, and antigen-loading efficiency. Engineered BMVs incorporating protein or mRNA antigens may further enhance antigen presentation and CD8⁺ T cell responses. This review summarizes the biological features, immunological mechanisms, and future potential of BMVs in vaccine development. Full article

Background: Oral colon-targeted delivery for inflammatory bowel disease (IBD) faces significant challenges, including limited gastrointestinal stability, premature drug release, and insufficient mucosal retention. Methods: To address these limitations, a mucoadhesive polysaccharide-based composite hydrogel incorporating prednisolone-loaded polymeric micelles was developed to enhance colonic delivery and promote mucosal repair. Amphiphilic oxidized dextran–oleylamine (ODEX-OA) copolymers were synthesized to self-assemble into prednisolone-loaded micelles. These micelles were subsequently embedded within a thiolated chitosan (CSSH) hydrogel through a Schiff base reaction, yielding the ODEX-OA-Pred-CSSH composite. The resulting system was comprehensively characterized for particle size, mucoadhesion, degradation, and pH/ROS dual-responsive drug release. Its colon-targeting capability and therapeutic efficacy were subsequently assessed in a dextran sulfate sodium (DSS)-induced colitis mouse model. Results: In vitro, the composite hydrogel demonstrated nanoscale micellar size, enhanced drug release kinetics under simulated inflammatory colonic conditions, and prolonged colonic retention for up to 24 h following oral administration. In vivo, studies confirmed that ODEX-OA-Pred-CSSH significantly alleviated colitis, evidenced by a reduced disease activity index, diminished pro-inflammatory cytokine levels, restored colon length, decreased spleen index, and improved histological mucosal repair. Conclusions: These findings collectively suggest that this mucoadhesive micelle–hydrogel composite represents a promising and effective oral colon-targeted platform for the treatment of IBD. Full article

Background: Macrophages were long regarded as passive executors of erythrophagocytosis responsible for systemic iron recycling. However, increasing evidence has reframed them as immunometabolic hubs that sense diverse environmental cues to modulate systemic iron homeostasis. Main body: This review examines the molecular architecture underlying macrophage iron metabolism and outlines how iron metabolic processes are dynamically regulated across spatial and temporal scales through the integration of mechanotransductive, mitochondrial, and epigenetic signaling pathways. Across disease contexts, macrophage iron handling displays marked heterogeneity, exemplified by contact-dependent iron transfer in tumors and ferroptosis-driven instability in cardiovascular disease. In cardiovascular pathologies, iron overload is associated with enhanced ferroptosis-related cascades that contribute to atherosclerotic plaque instability. Furthermore, at mucosal interfaces, host–pathogen competition over nutritional immunity highlights epigenetic strategies by which pathogens perturb host iron machinery. Conclusions: Linking these mechanistic insights to clinical translation, emerging therapeutic strategies are discussed that move beyond non-specific systemic iron chelation toward more targeted interventions. These include engineering macrophages for targeted drug delivery, exploiting nanomedicine-based redox modulation to influence macrophage phenotypes, and non-invasive regulation via the gut microbiota–epigenetic axis. Collectively, elucidating macrophage iron metabolic networks provides a conceptual framework for the development of precision approaches to inflammatory, metabolic, and malignant diseases. Full article

S-methylmethionine (SMM, also known as vitamin U) is a sulfur-containing vitamin-like compound that has been investigated since the 1940s for its gastroprotective and cytoprotective properties. Historically derived from observations of antiulcer activity in plant-derived foods, SMM has been studied in preclinical models and limited clinical settings for its multilevel pharmacological effects. This narrative review critically evaluates the available evidence on SMM’s pharmacological actions across organ systems, with explicit differentiation between preclinical and clinical data. It covers the most consistently reported gastroprotective and antiulcer effects, as well as antioxidant, anti-inflammatory, cytoprotective, and regenerative activities observed predominantly in preclinical studies. Particular attention is paid to organ-specific protection in the nervous system, liver, kidneys, lungs, skin, eyes, and oral tissues, although human evidence remains scarce. Proposed mechanisms are mediated primarily through suppression of oxidative stress, modulation of inflammatory and immune responses, maintenance of glutathione homeostasis, activation of ERK/NF-κB and Nrf2/Keap1 pathways, and regulation of methylation processes. Building on recent descriptive reviews, this work provides a structured critical synthesis that grades evidence quality, compares SMM with the structurally related methyl donor S-adenosylmethionine (SAMe), and analyses the translational and regulatory barriers that have prevented Western drug registration despite over 70 years of investigation. Despite a substantial preclinical evidence base and historical clinical observations, the level of evidence for many indications remains limited. Well-designed Phase II randomized controlled trials and innovative pharmaceutical formulations (especially topical and mucosal delivery systems) are urgently needed to translate preclinical promise into clinical benefits. Full article