Search Results (1,398)

Background: To examine the antioxidant and anti-inflammatory effects of sitagliptin in restoring the intestinal mucosal barrier in rats with colitis induced by dextran sulfate sodium (DSS). Methods: Male Sprague-Dawley rats were administered 5% DSS in their drinking water to induce colitis. Sitagliptin was administered intragastrically at a dose of 15 mg/kg/day for a duration of eight days. Changes in the colon tissue were histologically examined, and the disease activity index (DAI) score was measured. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were evaluated. Gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, tight junction proteins occludin and ZO-1 was assessed. Levels of SGOT, SGPT, and serum iron were also measured. Results: Sitagliptin diminished DAI and histological index scores, as well as MDA levels, while augmenting SOD, GPx, and catalase levels over an eight-day period. Based on proinflammatory cytokines, sitagliptin reduced colon inflammation. Compared to the untreated DSS group, sitagliptin increased serum iron and lowered SGOT and SGPT. Conclusions: The present results indicate that administering sitagliptin orally for a week could aid in the recovery from DSS-induced colitis by reducing oxidative stress and pro-inflammatory cytokines. Additional studies are required to make this applicable for patients suffering from colitis. Full article

This study aimed to evaluate the protective effects of soluble dietary fiber (SDF) derived from Polygonatum cyrtonema Hua residues on cyclophosphamide (CTX)-induced intestinal injury in mice. A total of 60 C57BL/6 mice (6–8 weeks old; body weight, 23.8 ± 0.5 g) were randomly allocated to six groups (n = 10 per group): a control group (CON), a CTX model group (CTX), a levamisole-treated positive control group (PC), and low-, medium-, and high-dose SDF groups (125, 250, and 500 mg/kg body weight, respectively). Mice received oral administration of SDF or an equal volume of water for 21 consecutive days and were intraperitoneally injected with CTX (80 mg/kg body weight) on days 19–21 to induce intestinal injury. The results demonstrate that SDF possessed a porous, sponge-like network structure and comprised multiple monosaccharides. SDF intervention, particularly at medium and high doses, significantly attenuated CTX-induced body weight loss and immune organ atrophy; restored villus height and the villus-to-crypt ratio; increased the numbers of goblet cells and intraepithelial lymphocytes; elevated intestinal levels of sIgA, β-defensins, and lysozyme; and reduced serum levels of LPS, D-lactic acid, and DAO (p < 0.05). In conclusion, SDF derived from Polygonatum cyrtonema effectively mitigates CTX-induced intestinal injury by enhancing intestinal mucosal immunity and preserving intestinal barrier integrity, thereby highlighting its potential as a functional ingredient for promoting gut health. Full article

Background/Objectives: Oral mucositis (OM) is a common complication in laryngeal cancer (LC), during radiotherapy (RT), significantly affecting patient outcomes. Identifying sensitive biomarkers to predict OM severity is therefore crucial. MicroRNAs, which regulate inflammatory pathways involved in OM, are promising candidates. This retrospective study aimed to evaluate plasma miRNA-548L as a predictive biomarker for the occurrence and severity of OM in LC patients undergoing RT. Methods: The expression levels of the selected miRNAs were analyzed in plasma samples obtained from 76 LC patients prior to the initiation of RT. Bioinformatics analyses were performed to identify molecular pathways regulated by miRNA-548L and their potential link to the pathogenesis of OM. Results: Significantly decreased levels of the studied miRNA were observed in the plasma of LC patients who developed severe OM after the IV^th (p < 0.001), V^th (p = 0.039), VI^th (p < 0.001), and VII^th (p < 0.001) cycles of RT. Additionally, the expression of miRNA-548L enabled reliable differentiation between patients who developed severe OM during the IV^th (AUC = 0.81, p < 0.001), V^th (AUC = 0.77, p < 0.001), VI^th (AUC = 0.82, p < 0.001), and VII^th (AUC = 0.86, p < 0.001) weeks of treatment. Importantly, lower expression of miRNA-548L (HR = 3.12; p = 0.010) was significantly associated with shorter median overall survival (OS). Conclusions: Pretreatment plasma miRNA-548L shows potential as a biomarker for predicting severe OM in LC patients undergoing RT. Notably, reduced miRNA-548L expression is associated with shorter OS and may help stratify patients by OM severity. Full article

Background: Vaping has become one of the most prevalent risk behaviors among adolescents and young adults worldwide. Although electronic cigarettes (ECs) are often perceived as safer than conventional tobacco, concerns regarding their impact on oral health are increasing. This systematic review aimed to critically evaluate and synthesize the available evidence regarding the association between e-cigarette use and oral health outcomes in adolescents and young adults. Methods: A systematic search of PubMed/MEDLINE, EMBASE, Scopus, and EBSCOhost databases was conducted for observational studies published within the last ten years. Studies evaluating oral health outcomes among adolescents and young adults were included. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Tool for Analytical Cross-Sectional Studies, and certainty of evidence was graded using the GRADE approach. Results: Eight observational studies met the inclusion criteria and were included in the qualitative synthesis. E-cigarette use was associated with increased caries risk, higher prevalence of gingival inflammation, alterations in salivary flow and pH, changes in oral microbiota—including increased levels of Porphyromonas gingivalis—and elevated frequencies of micronuclei in oral mucosal cells. Four studies were rated as having low risk of bias and four as moderate risk. The overall certainty of evidence was low for all outcomes due to methodological limitations, heterogeneity in outcome assessment, and inadequate control of confounding factors, including dual use of combustible tobacco products. Conclusions: Current evidence may suggest a possible association between e-cigarette use and adverse oral health alterations in adolescents and young adults. However, given the low certainty of evidence, residual confounding, and the predominance of cross-sectional designs, causal relationships cannot be established. Well-designed longitudinal studies that clearly differentiate exclusive e-cigarette users from dual users and adequately adjust for behavioral confounders are required to clarify the independent impact of vaping on oral health in this vulnerable population. Full article

Background/Objectives: The neutrophil-to-lymphocyte ratio (NLR) is a simple biomarker reflecting systemic inflammatory status and has been investigated in head and neck cancer (HNC) as a potential prognostic indicator. Its role in relation to radiotherapy-related toxicity remains uncertain. The aim of this study was to provide a descriptive evaluation of NLR values in relation to oral mucositis severity and swallowing-related quality of life in patients undergoing radiotherapy-based treatment. Methods: We retrospectively evaluated 32 patients with locally advanced HNC treated with radiotherapy, with or without concomitant chemotherapy, in the definitive or adjuvant setting (March 2025–January 2026). NLR was calculated at baseline (T0), at a predefined mid-treatment timepoint (T3), and during week 6 of treatment (T6). Mucositis severity was assessed using CTCAE and the Oral Mucositis Assessment Scale (OMAS), while swallowing-related quality of life was measured using the MD Anderson Dysphagia Inventory (MDADI). Relationships between NLR values and toxicity endpoints were descriptively assessed using Spearman correlation analysis. Results: No statistically significant correlations were observed between NLR values and OM severity or swallowing-related outcomes at any evaluated timepoint. At T3, non-significant correlations were observed between NLR and CTCAE mucositis grade and between NLR and MDADI global score. No statistically significant correlations were observed between NLR values and OMAS at any evaluated timepoint. Conclusions: In this retrospective cohort, no association between NLR and radiotherapy-related mucositis severity or swallowing-related quality of life was demonstrated. These findings are descriptive and limited by the small sample size, the retrospective design, and the absence of control for potential confounding factors. No inferential or causal conclusions can be drawn. Further prospective studies with larger and more homogeneous cohorts are required to better characterize NLR behavior in this clinical setting. 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

Background: Potentially malignant oral disorders (OPMDs) and oral carcinomas represent a significant oncological concern in incarcerated populations, where multiple modifiable risk factors such as tobacco use, illicit drug consumption, oncogenic human papillomavirus infections, and poor oral hygiene coexist with limited access to preventive and routine dental care. This combination may increase the risk of delayed diagnosis and malignant transformation. Objective: This PRISMA-compliant systematic review aimed to evaluate the prevalence of OPMDs and associated risk factors in prison populations, with a particular focus on identifying gaps in the current evidence. Methods. A systematic literature search was conducted in PubMed, Scopus and Cochrane Library using predefined search strategies. The final search yielded 24 records, which were screened according to PRISMA 2020 guidelines. After title and abstract screening, 10 full-text articles were assessed for eligibility, and 5 cross-sectional studies were included in the qualitative synthesis following independent review. Results: The included studies revealed a substantial burden of oral mucosal lesions in incarcerated populations. Premalignant lesions were reported in a significant proportion of inmates, with oral submucous fibrosis particularly prevalent in some cohorts. Additionally, a high prevalence of oral high-risk HPV infection and widespread oral manifestations were observed. Tobacco use, often combined with betel quid, alcohol, or illicit drugs, emerged as the primary and consistently associated risk factor for oral lesions. Conclusions: Prison populations appear to represent a high-risk group for OPMDs due to the combined effect of behavioral and structural risk factors. However, the limited number of available studies, their cross-sectional design, and methodological heterogeneity prevent definitive conclusions. Further longitudinal and methodologically robust studies are needed to better define prevalence patterns and support targeted screening and prevention strategies in correctional settings. Full article

Background and Objectives: Prolonged contact between oral mucosa and dental amalgam restorations may influence local epithelial homeostasis, but the remodeling profile of clinically non-dysplastic mucosa exposed to long-standing amalgam remains insufficiently characterized. This study aimed to evaluate histopathological changes and CK19, Ki67, and p53 expression in the oral mucosa adjacent to long-term amalgam restorations. Materials and Methods: A retrospective observational analysis was performed on 108 oral mucosal specimens, including 78 samples in direct contact with amalgam restorations and 30 non-exposed controls. Exposed cases were grouped according to contact duration: 5–10 years, 11–20 years, and ≥21 years. Histopathological parameters and immunohistochemical expression of CK19, Ki67, and p53 were semi-quantitatively assessed, and an exploratory Integrated Epithelial Remodeling Score was calculated. Results: Longer amalgam exposure was significantly associated with increased inflammatory infiltrate, basal hyperplasia, acanthosis, fibrosis, suprabasal CK19 redistribution, and higher Ki67 labeling indices. The Integrated Epithelial Remodeling Score differed significantly among exposure groups, with higher values in intermediate- and long-duration exposure categories. p53 expression showed statistically detectable but heterogeneous variation. No epithelial dysplasia was observed. Conclusions: Long-term contact with dental amalgam restorations was associated with a coordinated, non-dysplastic remodeling phenotype of the oral mucosa. Given the age imbalance across exposure duration groups, these findings should be interpreted as exposure-associated patterns rather than evidence of a direct causal effect. Because no comparison group exposed to other restorative materials was included, material-specificity for dental amalgam cannot be inferred. In architecturally preserved mucosa, suprabasal CK19 expression may reflect adaptive epithelial plasticity rather than preneoplastic transformation. 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

This study investigated the gastroprotective effects of Salvia plebeia extract (SPE) against acute gastric mucosal injury induced by 150 mM HCl/60% ethanol in rats and explored its antioxidant and anti-inflammatory mechanisms. SPE exhibited strong in vitro antioxidant activity, with DPPH and ABTS radical scavenging rates of 86.2 ± 2.4% and 89.1 ± 1.9%, respectively, along with a high total polyphenol content (96.4 ± 3.1 mg gallic acid equivalents/g extract). In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, SPE attenuated LPS-induced inflammatory signaling, as evidenced by reduced TLR4 and JNK expression and restoration of IκBα levels. In vivo, oral administration of SPE (100 or 300 mg/kg) 1 h prior to HCl/ethanol challenge significantly reduced gastric lesion area and improved histopathological damage compared with the HCl/ethanol-treated control group. SPE also increased gastric pH, reduced gastric juice volume, decreased serum levels of TNF-α and IL-6, and downregulated gastric mucosal mRNA expression of Nos2 and Ptgs2. Immunohistochemical analysis further showed that SPE attenuated NF-κB p65 immunoreactivity in gastric tissues. Collectively, these findings suggest that SPE exerts gastroprotective effects through antioxidant activity and suppression of inflammatory responses associated with the MAPK/NF-κB pathway in acute HCl/ethanol-induced gastric injury. Full article

Oral mucosal and periodontal diseases are commonly associated with persistent inflammation, oxidative stress, impaired wound healing, and reduced oral health-related quality of life. Nano-Bio Fusion (NBF) gingival gel is a bioadhesive nano-formulated oral gel containing propolis, vitamin C, and vitamin E, developed for local application under oral soft tissue conditions. This critical narrative review aimed to evaluate the currently available evidence regarding the clinical applications, safety profile, and therapeutic potential of NBF gel in oral soft tissue therapy. A structured non-systematic literature search was performed using PubMed, Embase, Cochrane Library, and Google Scholar, and 16 relevant studies were included. The available evidence suggests that NBF gel may provide clinical benefits as an adjunct to non-surgical periodontal therapy, with reported improvements in plaque and gingival indices, periodontal probing depth, clinical attachment level, wound healing, and pain-related outcomes. In addition, potential beneficial effects have been reported in oral surgery-related wound healing, alveolar osteitis, desquamative gingivitis, erosive lichen planus, and xerostomia-associated mucositis. Several studies reported outcomes comparable to conventional therapies, including chlorhexidine-based regimens and locally delivered antimicrobials; however, the evidence remains heterogeneous and limited. Furthermore, the proposed biological mechanisms, including antioxidant, antimicrobial, and tissue-modulating effects, are not yet fully supported by mechanistic or pharmacokinetic evidence. The currently available literature is limited by heterogeneity in study design, small sample sizes, short follow-up periods, and limited independent validation. Therefore, further well-designed, adequately powered randomized controlled trials with standardized methodologies are required to better define the clinical role of NBF gel in evidence-based oral soft tissue therapy. Full article

Aim: Asthma is a chronic condition with high prevalence in pediatric populations and may negatively influence oral health. The primary aim of this study was to evaluate the association between asthma and oral health-related quality of life (OHRQoL) in Portuguese children aged 6 to 8 years. Secondary aims included comparing caries experience, salivary parameters, and other clinical oral health indicators between asthmatic and non-asthmatic peers. Materials and Methods: A cross-sectional study was conducted with 89 child–parent pairs using a convenience sampling approach. Children with asthma were recruited from a hospital immunoallergology service, and healthy controls were recruited from a primary school. Data collection included parent-administered questionnaires on sociodemographic and behavioral factors, the Portuguese version of the SOHO-5 (child self-report and parent proxy forms), and standardized intraoral examinations assessing caries (WHO criteria, 5th edition), malocclusion, gingival bleeding, dental erosion, mucosal lesions, and molar–incisor hypomineralization. Stimulated salivary flow was measured. Bivariate statistical analyses and multivariable regression models were performed using SPSS (v.29), with a significance level set at p < 0.05. Results: Asthmatic children had significantly higher caries prevalence in both primary (52.6% vs. 27.5%, p = 0.027) and permanent dentition (32.4% vs. 0%, p < 0.001), as well as higher mean dmft scores (2.68 vs. 1.14, p = 0.026), reduced stimulated salivary flow (78.9% vs. 41.2% with low flow, p < 0.001), and worse child-reported SOHO-5 scores (mean 2.42 vs. 1.25, p = 0.004). After multivariable adjustment, asthma remained a significant independent predictor of low salivary flow (OR = 4.017, 95% CI: 1.443–11.178, p = 0.008), while the association with caries was attenuated and no longer significant (OR = 1.345, p = 0.590). Pain experience in the past year was the strongest predictor of OHRQoL across all multivariable models (SOHO-5 child: B = 1.583, p = 0.006; SOHO-5 total: B = 4.970, p < 0.001), indicating that children with pain history reported substantially worse OHRQoL. After adjustment, asthma did not reach statistical significance for either child-reported (B = 0.732, p = 0.090) or total OHRQoL scores (B = 0.693, p = 0.293). These findings should be interpreted cautiously given the limited number of covariates included in the models, constrained by the available sample size. Conclusions: Within the limitations of this cross-sectional study, including a small and non-probabilistic sample, asthmatic children presented a higher caries burden and a markedly higher prevalence of low stimulated salivary flow compared with non-asthmatic peers. Asthma remained a significant independent predictor of low salivary flow after multivariable adjustment, while the association with caries was attenuated, suggesting partial confounding by dietary habits. These findings highlight the importance of integrating oral health surveillance into the routine care of asthmatic children, with particular attention paid to salivary function and caries prevention. Full article

Background/Objectives: Burning Mouth Syndrome (BMS) is a chronic condition characterized by recurrent oral burning in the absence of visible mucosal lesions. Although its etiology is multifactorial and not fully understood, recent evidence suggests that alterations in masticatory function and occlusal patterns may contribute to symptom development and persistence. The aim of this review is to explore the association between BMS and alterations in masticatory and occlusal function and perception. Methods: A scoping review was conducted using PubMed, Cochrane, Web of Science, and Scopus databases. The search covered studies published between January 1988 and February 2026. Inclusion criteria included studies in English addressing the relationship between BMS and masticatory or occlusal function and perception. Search strategy included both primary and review studies, and excluded congress abstracts and proceedings, commentaries, letters, theses/dissertations, editorials, animal and preclinical studies. Results: Thirteen studies met the inclusion criteria and were grouped into three categories: occlusal perception and sensory alterations (n = 4), dysfunctional oral habits (n = 6), and prosthetic factors (n = 3). Findings, presented descriptively, suggest that BMS patients may exhibit altered occlusal and sensory perception, increased sensitivity to mechanical or thermal stimuli, and possible central pain dysregulation. Dysfunctional or parafunctional habits may also be associated with symptom persistence. Additionally, prosthetic factors were reported in some studies to be linked with oral discomfort, with symptom improvement following corrective interventions in selected cases. Conclusions: BMS appears to be a complex and multifactorial condition. Altered sensory perception, parafunctional habits, and prosthetic factors may contribute to symptom expression. However, the available evidence is heterogeneous and limited; therefore, further well-designed longitudinal and interventional studies are needed before definitive conclusions can be drawn. Full article

Background/Aim: This study aims to assess the prevalence of self-reported oral ulcers and their associated factors among patients with type 2 diabetes mellitus (T2DM) in Bangladesh. Materials and Methods: A hospital-based cross-sectional study was conducted among 260 patients with T2DM attending outpatient dental services at three tertiary hospitals in Dhaka. Data were collected using a semi-structured questionnaire covering sociodemographic characteristics, behavioral and dietary factors, medical history, and self-reported oral mucosal conditions. Associations between oral ulcers and potential risk factors were analyzed using Chi-square and Fisher’s exact tests. Results: Most participants were middle-aged (50–59 years), female, of low educational status and married, with a high prevalence of regular tooth-brushing but low use of oral hygiene aids such as mouthwash. Traumatic ulcers (21.5%) and oral lichen planus (19.6%) were the most frequently observed oral mucosal lesions followed by recurrent aphthous ulcers, oral lichenoid reactions, and oral candidiasis. Traumatic ulcers and oral lichenoid reactions showed associations with sharp teeth, dentures or braces, and amalgam restorations, while lichen planus and aphthous ulcers were significantly associated with smoking, systemic conditions such as hypertension, and coexisting oral lesions such as oral candidiasis. Multivariable logistic regression showed that sharp teeth, denture or brace use, amalgam restorations, and tobacco-related habits were associated with oral lesions. Conclusions: Oral ulcers and related mucosal lesions were found to be common among patients with T2DM in Bangladesh, with traumatic ulcers being most frequent and several local and behavioral factors showing significant associations. 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