Drug Design, Development and Therapy最新文献

{"title":"Cipepofol versus Conventional Sedation for Pneumonia Patients Receiving Mechanical Ventilation: A Real-World Retrospective Study of Effectiveness and Hemodynamic Safety.","authors":"Yuanyuan Li, Hao Zhou, Hongqian Qin, Wei Yang, Yanhao Wu, Wenzhong Peng, Juan Jiang","doi":"10.2147/DDDT.S627449","DOIUrl":"https://doi.org/10.2147/DDDT.S627449","url":null,"abstract":"<p><strong>Purpose: </strong>Severe pneumonia often necessitates invasive mechanical ventilation (MV) and prolonged sedation in the ICU. This real-world retrospective cohort study aimed to compare cipepofol vs conventional sedation regimens in this vulnerable population, with MV duration as the primary endpoint and hemodynamic safety as a key safety outcome.</p><p><strong>Patients and methods: </strong>This retrospective cohort study evaluated mechanically ventilated patients with severe pneumonia who received continuous sedation for more than 48 hours. Patients were classified into cipepofol or conventional sedation (propofol-, midazolam- or dexmedetomidine-based) groups. Propensity score matching (PSM) was performed at a 1:1 ratio based on age and APACHE II scores.</p><p><strong>Results: </strong>After PSM, 198 patients (99 per group) were analyzed. The primary endpoint<b>-</b>MV duration did not differ significantly between the cipepofol and conventional groups (median 218.23 vs 227.25 hours, <i>P</i> = 0.740). Subgroup analysis further confirmed that there was no significant difference in MV duration between propofol- and midazolam-based regimens compared to the cipepofol-regimen. Notably, cipepofol demonstrated superior hemodynamic safety, showing significantly lower incidences of early hypotension within the first hour (11.1% vs 27.3%, <i>P</i>=0.007) and overall bradycardia (19.1% vs 36.1%, <i>P</i>=0.014). Post-hoc subgroups analysis revealed that cipepofol reduced the risks of early hypotension and overall bradycardia compared to propofol- or midazolam-based regimens in hospital-acquired pneumonia patients. Multivariate analysis confirmed cipepofol use as an independent protective factor against early hypotension (adjusted OR 0.300, 95% CI: 0.136<b>-</b>0.665, <i>P</i>=0.003) and bradycardia (adjusted OR 0.414, 95% CI: 0.212<b>-</b>0.808, <i>P</i>=0.010). No significant differences were found regarding sedation success, length of ICU stay, 28-day ventilator-free days, 28-day mortality, vasopressor requirements, or organ function parameters (all <i>P</i>>0.05).</p><p><strong>Conclusion: </strong>In mechanically ventilated patients with severe pneumonia requiring prolonged sedation, cipepofol did not shorten MV duration compared with propofol- or midazolam-based conventional regimens, but it significantly reduced risks for early hypotension and overall bradycardia events.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (NCT06514781).</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"627449"},"PeriodicalIF":6.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concerns Regarding the Interpretation of Real-World Safety and Effectiveness Results for Imrecoxib [Letter].","authors":"Keyuan Fang","doi":"10.2147/DDDT.S658072","DOIUrl":"https://doi.org/10.2147/DDDT.S658072","url":null,"abstract":"","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"658072"},"PeriodicalIF":6.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leucine Mitigates Diabetic Nephropathy via Its Antioxidant Effect and Modulation of TGF-β/SMAD-3 Signalling Pathway in Streptozotocin-Induced Diabetic Rats.","authors":"Zekrayat J H Merdas, Mahmoud A Bekhit, Reem M Hazem, Enas S Gad, Nuseibah Al Qtaish, Alanoud F Alsumait, Norhan M El-Sayed","doi":"10.2147/DDDT.S619144","DOIUrl":"https://doi.org/10.2147/DDDT.S619144","url":null,"abstract":"<p><strong>Background/objectives: </strong>Diabetic nephropathy (DN) is the main contributor to the incidence of end-stage renal disease and kidney failure. This research aims to explore the curative effect of leucine in the DN rat model.</p><p><strong>Methods: </strong>40 male rats were sorted into four equal groups. Group I acted as the control group. Group II was given leucine (1.35g/kg orally, once daily) for 8 weeks. Group III administered a single intraperitoneal injection of Streptozotocin (STZ) (45 mg/kg, i.p.). Group IV was administered leucine following the diagnosis of diabetes for a duration of 8 weeks. In this study, samples were obtained from blood and renal tissue for biochemical assessments, evaluation of redox state, real-time polymerase chain reaction (RT-PCR) analysis of L-type amino acid transporter 1 (LAT1) and suppressor of Mothers against Decapentaplegic (SMAD3) genes, as well as histological examination.</p><p><strong>Results: </strong>Leucine supplementation to diabetic rats markedly reduced alterations in markers of kidney function. Furthermore, a reduction in redox markers and inflammatory cytokines was observed in tissues isolated from the leucine-treated diabetic group compared with diabetic rats. Additionally, the expression of the SMAD3 gene, mTOR, and c-JNK protein in renal tissue was significantly reduced in the leucine-diabetic group compared with the diseased group. Conversely, LAT1 tissue expression was upregulated in the leucine-diabetic group.</p><p><strong>Conclusion: </strong>The administration of leucine inhibited renal damage by reducing activation of the profibrotic transforming growth factor beta-1 TGF-β/Smad3 signalling pathway.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"619144"},"PeriodicalIF":6.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Ciprofol- versus Remimazolam-Based Total Intravenous Anesthesia on Postoperative Nausea and Vomiting After Laparoscopic Cholecystectomy: A Randomized Controlled Trial.","authors":"Jinfang Zeng, Ying Ye, Zijian Li, Shu Yang, Jinjin Jian, Dongxiao Huang","doi":"10.2147/DDDT.S624552","DOIUrl":"https://doi.org/10.2147/DDDT.S624552","url":null,"abstract":"<p><strong>Background: </strong>Postoperative nausea and vomiting (PONV) remains common after laparoscopic cholecystectomy. Whether ciprofol-based anesthesia reduces PONV compared with remimazolam-based anesthesia remains unclear.</p><p><strong>Methods: </strong>In this single-center, randomized, assessor-blinded, parallel-group trial, adults undergoing laparoscopic cholecystectomy were assigned to receive ciprofol- or remimazolam-based total intravenous anesthesia. All participants received standardized antiemetic prophylaxis with dexamethasone and ondansetron, together with a standardized analgesic protocol. The primary outcome was the cumulative incidence of PONV within 24 h after surgery. Secondary outcomes included nausea, vomiting, rescue antiemetic use, postoperative pain, QoR-15 score, adverse events, and intraoperative hemodynamic variables.</p><p><strong>Results: </strong>A total of 146 patients were randomized, with 73 patients in each group. The incidence of PONV within 24 h was lower in the ciprofol group than in the remimazolam group [23/73 (31.5%) vs 43/73 (58.9%); RR 0.53, 95% CI 0.36-0.79; P = 0.001]. This association remained significant after adjustment for clinically relevant PONV risk factors(adjusted OR 0.289, 95% CI 0.135-0.623; P = 0.002). Ciprofol was also associated with lower incidences of nausea, vomiting, and rescue antiemetic use. Postoperative pain, QoR-15 score, overall adverse events, and vasopressor use were similar between groups.</p><p><strong>Conclusion: </strong>Under a standardized prophylactic antiemetic protocol, ciprofol-based total intravenous anesthesia was associated with a lower 24-h incidence of PONV than remimazolam-based anesthesia in adults undergoing laparoscopic cholecystectomy. No statistically significant between-group differences were observed in postoperative recovery measures, adverse events, or vasopressor use; however, the trial was not powered to establish equivalence for these secondary or safety outcomes. Further multicenter studies are needed to confirm the robustness and generalizability of this finding across different multimodal antiemetic strategies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"624552"},"PeriodicalIF":6.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous Quantification of Vedolizumab, Ustekinumab, and Infliximab in Human Serum by LC-MS/MS: Application to Therapeutic Drug Monitoring in Inflammatory Bowel Disease.","authors":"Yanbao Zhang, Na Wang, Weiyang Zheng, Ruichen Liu, Limei Li, Xianglong Zhao, Xin Zheng, Xiaohong Han","doi":"10.2147/DDDT.S632769","DOIUrl":"https://doi.org/10.2147/DDDT.S632769","url":null,"abstract":"<p><strong>Purpose: </strong>With the expanding use of therapeutic monoclonal antibodies (mAbs) in inflammatory bowel disease (IBD), there is a critical need for robust, multiplex analytical tools to support therapeutic drug monitoring (TDM) and pharmacokinetic studies. This study aimed to develop and validate a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of infliximab (IFX), vedolizumab (VDZ), and ustekinumab (UST) in human serum.</p><p><strong>Patients and methods: </strong>A universal immunocapture strategy utilizing Protein G magnetic beads was used to enrich total IgG from human serum. Samples were subjected to tryptic digestion and analyzed in multiple reaction monitoring (MRM) mode, with rituximab as a full-process internal standard. Method validation was performed in accordance with regulatory guidelines, evaluating linearity, precision, accuracy, selectivity, recovery, matrix effect, and stability. The validated method was subsequently applied to residual serum samples from IBD patients undergoing treatment.</p><p><strong>Results: </strong>The method demonstrated excellent linearity (R²>0.99) over the concentration ranges of 0.5-100 μg/mL for IFX and UST, and 1-200 μg/mL for VDZ. Total precision ranged from 1.1% to 14.9%, and accuracy ranged from -12.1% to 14.5%. Validation parameters, including selectivity, carryover, recovery, matrix effects, dilution integrity, and stability, were all within acceptable criteria. Analysis of the 37 clinical samples revealed marked inter-individual variability in drug concentrations. However, the absence of key covariates (eg, body weight and dosing history) precluded a formal pharmacokinetic analysis or attribution of this variability to specific clinical factors.</p><p><strong>Conclusion: </strong>The developed LC-MS/MS method provides a practical, specific, and reproducible tool for the multiplex quantification of therapeutic mAbs. Based on a preliminary exploratory study of 37 patient samples, this method demonstrates analytical feasibility and serves as a promising tool for pharmacokinetic research; however, its definitive clinical applicability and readiness for routine TDM require further confirmation through cross-platform comparison, incurred sample reanalysis, and external validation in larger cohorts.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"632769"},"PeriodicalIF":6.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening and Determination of Biomarkers and Their Associated Active Components for Enhanced Therapeutic Effect of Exocarpium Citri Grandis-Folium Ginkgo Couplet on Liver Injury Caused by Hyperlipidemia via UPLC-TOF-MS and UPLC-MS.","authors":"Caihui Liu, Guangying Wu, Xingqin Wei, Guanlin Xiao, Zhao Chen","doi":"10.2147/DDDT.S636596","DOIUrl":"https://doi.org/10.2147/DDDT.S636596","url":null,"abstract":"<p><strong>Introduction: </strong>The combination of Exocarpium Citri Grandis-Folium Ginkgo (E-GC) demonstrates superior therapeutic effects on liver injury caused by hyperlipidemia compared with individual use; however, accurate and quantifiable indicators for evaluating the efficacy and quality of the couplet remain lacking. Reliance solely on changes in certain differential metabolites or the bioavailability of chemical components is insufficient to confirm the superior efficacy of the couplet.</p><p><strong>Methods: </strong>In this study, a rat model of liver injury caused by hyperlipidemia was used to verify the enhanced efficacy of E-GC. Subsequently, network pharmacology combined with molecular biology validation was applied to identify the primary regulatory targets. The results were integrated with UPLC-TOF-MS, UPLC-MS and database analyses to identify biomarkers indicating the enhanced efficacy of E-GC, as well as serum concentrations of active components in E-GC to quantitatively evaluate the effect of the couplet on their bioavailability. Finally, correlation statistical analyses were conducted on the above-mentioned data to confirm that the identified biomarkers and significantly altered active components can characterize the enhanced efficacy of the couplet.</p><p><strong>Results: </strong>Metabolomics analysis identified 59 related metabolites, among which arachidonic acid, choline, deoxycholic acid, N-acetylserotonin, and cholic acid significantly increased in the liver following E-GC treatment, with similar changes observed in serum levels (p<0.05). A total of 36 components were identified, apigenin, naringin, and ginkgolide A/B/C exhibited significantly increased bioavailability after combination (p<0.05). These changes were closely associated with the improved regulation of PXR-FXR expression by E-GC compared with individual use, and E-GC also exerted strong regulatory effects on downstream targets, such as LXR, FGF1, ABCB1b, and ERK.</p><p><strong>Conclusion: </strong>Through the above analyses, in order to solve the problem of lacking accurate and quantifiable indexes to evaluate the effect of TCM couplet, a method was successfully established for evaluating the enhanced efficacy of E-GC in treating liver injury caused by hyperlipidemia, and the principal biomarkers and quality control indicators based on active components were identified.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"636596"},"PeriodicalIF":6.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amorphous Solid Dispersions for BCS Class II Antihyperlipidemic Drugs: From Drug-Polymer Interactions to in vivo Performance.","authors":"Sucilawaty Ridwan, Rimadani Pratiwi, Suci Zulaikha Hildayani, Arif Budiman","doi":"10.2147/DDDT.S634131","DOIUrl":"https://doi.org/10.2147/DDDT.S634131","url":null,"abstract":"<p><p>Hyperlipidemia is a major health concern worldwide, and oral therapies like statins, fibrates, and ezetimibe are severely limited by their poor water solubility, classified in the Biopharmaceutics Classification System (BCS) Class II. Although amorphous solid dispersion (ASD) technology shows promise in overcoming these biopharmaceutical limitations, a comprehensive synthesis linking molecular drug-polymer interactions to dissolution enhancement, pharmacokinetic performance, and preclinical in vivo efficacy remains underreported. Addressing this gap, this review comprehensively evaluates BCS Class II antihyperlipidemic ASD frameworks. A comprehensive literature search was conducted across PubMed, Scopus, ScienceDirect, and Google Scholar for studies published between 2015 and 2025 (n=16). ASD conversion significantly enhances dissolution kinetics via the \"spring and parachute\" mechanism. Specific molecular interactions, including hydrogen bonding and hydrophobic interactions with polymeric carriers, restrict molecular mobility and effectively inhibit recrystallization. Biopharmaceutical studies confirmed that these molecular pathways translate into improved systemic exposure in rodent dyslipidemia models, with significant increases in peak plasma concentration (<i>C_max</i> ) and area under the curve (<i>AUC</i>). In addition, preclinical pharmacodynamic studies typically show increased lipid-lowering efficacy, with significant reductions in total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) compared with pure crystalline medicines. Overall, although ASD formulations dramatically improve in vitro dissolution, pharmacokinetic characteristics, and preclinical performance, their clinical translational impact still needs full validation. Therefore, future studies should focus on human head-to-head clinical trials, long-term physical stability studies, and scalable manufacturing to enable the commercial translation of antihyperlipidemic ASDs.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"634131"},"PeriodicalIF":6.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Multi-Omics, Machine Learning, and Single-Cell Analysis Provide Insights into Potential Multi-Target Candidate Mechanisms of Combined MAGL11 and Icaritin in Alleviating Imidazole Propionate-Driven Metabolic Intestinal Injury.","authors":"Rongrong Wang, Qingzhou Meng, Xishuang Wang, Mingmin Jiang, Dejun Niu, Guofei Qin, Qun Feng, Yujun Tan, Xu Jiao, Mengdi Zhang, Liyuan Gong, Wenlong Yang, Yunshun Qiu, Jingchun Yao, Shirong Li, Ming Liu","doi":"10.2147/DDDT.S627608","DOIUrl":"https://doi.org/10.2147/DDDT.S627608","url":null,"abstract":"<p><strong>Background: </strong>Unhealthy diets, especially high red meat intake, induce gut dysbiosis and abnormal accumulation of a harmful histidine metabolite imidazole propionate (IMP), thereby promoting ulcerative colitis (UC) development. Although combined treatment with a MAGL inhibitor (MAGL11) and icaritin (Y003) exerts combined therapeutic effects in the classical DSS‑induced UC model, its protective effects and molecular mechanisms against IMP‑driven metabolic model remain unclear.</p><p><strong>Purpose: </strong>The present study was designed to evaluate the therapeutic effect of MAGL11 and Y003 on IMP‑driven metabolic intestinal injury model and to elucidate the associated molecular mechanisms.</p><p><strong>Methods: </strong>We evaluated the protective effects of MAGL11 and Y003 combination therapy in an IMP-induced intestinal injury model and integrated multi‑omics data to explore the underlying mechanisms.</p><p><strong>Results: </strong>In this short-term preclinical study in male mice, the combined treatment significantly alleviated UC symptoms, suppressed pro‑inflammatory cytokines, repaired the intestinal barrier, corrected metabolic disturbances, and reshaped the gut microbiota. Four hub genes were prioritized by machine learning integrating differential expression analysis and WGCNA of GEO data together with targets of MAGL11+Y003 and fecal metabolites. Molecular docking predicted favorable binding affinities between MAGL11/Y003 and the four target proteins (CA2, ABCB1, ABCG2, MMP3). Single‑cell analysis revealed cell‑type‑specific dysregulation of these genes. Furthermore, CA2, ABCB1, and ABCG2 were downregulated, while MMP3 was upregulated in the colon tissues of IMP‑induced model mice, while the combination therapy reversed these changes. Proteomics and Western blot validation indicated that the therapeutic efficacy of the combination treatment was associated with the suppression of the VEGF and MAPK pathway as well as the modulation of apoptosis- and metabolism-related pathways.</p><p><strong>Conclusion: </strong>Collectively, MAGL11 and Y003 combined therapy alleviates IMP‑driven metabolic intestinal injury through multi‑target, multi‑pathway actions with a greater therapeutic effect, offering a novel strategy for metabolically associated colitis and prioritizing CA2, ABCB1, ABCG2, and MMP3 as candidate treatment-responsive molecules requiring further functional validation.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"627608"},"PeriodicalIF":6.1,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Konjac Glucomannan as a Gel-Forming Biopolymer for Transdermal Drug Delivery: Properties, Formulation Strategies, and Translational Challenges.","authors":"Dian Arista Damayanti Asis, Yoga Windhu Wardhana, Anis Yohana Chaerunisaa","doi":"10.2147/DDDT.S632989","DOIUrl":"https://doi.org/10.2147/DDDT.S632989","url":null,"abstract":"<p><p>Konjac glucomannan is a natural polysaccharide increasingly relevant as a matrix forming material for skin applied delivery systems. Its potential is linked to its glucose and mannose backbone, abundant hydroxyl groups, partial acetyl substitution, high molecular weight, and capacity for chain association. These features regulate hydration, swelling, rheology, viscoelasticity, film formation, gelation, and drug release. This narrative review examines konjac glucomannan from a structure based formulation perspective, covering physicochemical attributes, modification strategies, formulation platforms, release behavior, and evaluation requirements. Unlike previous reviews that broadly discuss polysaccharide based transdermal systems or glucomannan across pharmaceutical applications, this review focuses on the relationship between KGM structure, formulation design, and translational performance. Evidence shows its use in films, hydrogel reservoirs, injectable hydrogels, nanofibrous systems, carrier assisted systems, and multilayer matrices. In these platforms, konjac glucomannan functions as a hydration regulating matrix former, release modulator, and structural component. Blending, deacetylation, oxidation, crosslinking, freeze thaw treatment, electrospinning, and layered design can improve mechanical integrity, moisture control, and release performance. However, outcomes vary with molecular attributes, modification conditions, and evaluation methods. Most studies remain focused on material characterization and in vitro release, while durable skin adhesion, ex vivo permeation, skin deposition, long wear performance, and clinically meaningful transport are still insufficiently demonstrated. Further translation requires standardized molecular attributes, ex vivo and in vivo testing, scalable manufacturing, and regulatory evaluation.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"632989"},"PeriodicalIF":6.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Initial Dosage Optimization of Tacrolimus in Connective Tissue Disease-Associated Interstitial Lung Disease Patients: An Exploratory Study.","authors":"Guan-Ying Zhang, Ying-Wei Jin, Jie Wang, Ke-Wen Ding, Shi-Yuan Zhao, Zhi-Hao Ping, Jia-Yi Du, Su-Mei He, Hai-Bo Zhang, Dong-Dong Wang","doi":"10.2147/DDDT.S620915","DOIUrl":"https://doi.org/10.2147/DDDT.S620915","url":null,"abstract":"<p><strong>Objective: </strong>Tacrolimus has emerged as a promising therapeutic agent for connective tissue disease-associated interstitial lung disease (CTD-ILD) patients. However, its clinical application is substantially hindered by high interindividual pharmacokinetic variability and a narrow therapeutic window, which poses critical challenges particularly for the formulation of the initial dosage regimen.</p><p><strong>Methods: </strong>A retrospective real-world study was conducted on 22 CTD-ILD patients receiving tacrolimus therapy. Comprehensive clinical data were systematically collected, encompassing demographic characteristics, routine physiological and biochemical parameters, and detailed concomitant medication records. A population pharmacokinetic (PPK) model for tacrolimus in CTD-ILD patients was developed using the nonlinear mixed-effects modeling approach implemented in NONMEM software. Monte Carlo simulation was subsequently performed to recommend the optimal initial dosage regimen of tacrolimus for CTD-ILD patients.</p><p><strong>Results: </strong>Based on the results of the model, we proposed initial dosing regimens: for CTD-ILD patients, the recommended initial tacrolimus dosage was 0.10 mg/kg across the body weight range of 50-100 kg, which yielded a target attainment probability of 89.1-93.5%, a probability below 5 ng/mL was 6.3-10.9%, a probability above 10 ng/mL was 0-0.2%.</p><p><strong>Conclusion: </strong>This was an exploratory single-center PPK analysis recommending the initial dosage of tacrolimus for CTD-ILD patients. We proposed the 0.10 mg/kg regimen as a preliminary model-derived starting dose, which warranted prospective validation and therapeutic drug monitoring (TDM). Given the inherent limitations including the relatively small sample size, lack of external validation, further large-scale prospective studies were warranted to confirm these conclusions.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"620915"},"PeriodicalIF":6.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}