Drug Delivery and Translational Research最新文献

{"title":"Targeted delivery of IFN-α-anti-GPC3 fusion protein via mRNA-LNP platform elicits potent anti-tumor immunity in hepatocellular carcinoma.","authors":"Yajie Pan, Ruyue Chen, Xueyan Lv, Yuehang Wang, Hongyu Zhang","doi":"10.1007/s13346-025-01911-y","DOIUrl":"https://doi.org/10.1007/s13346-025-01911-y","url":null,"abstract":"<p><p>This study aimed to utilize the mRNA-lipid nanoparticle (mRNA-LNP) platform to achieve in situ hepatic expression of an interferon-α (IFN-α)/anti-glypican-3 (anti-GPC3) fusion protein (GPA01), enhancing IFN-α targeting and antitumor activity to provide a precision therapy strategy for GPC3-positive hepatocellular carcinoma (HCC). mRNA encoding a GPC-3/IFN-α bispecific fusion protein was designed and synthesized, encapsulated in lipid nanoparticles, and transfected into HCC cell lines (HepG2) for in vitro characterization of protein expression, binding activity, and gene induction. Orthotopic HCC models (HepG2-luc) and subcutaneous tumor model (Hepa 1-6/hGPC3-hi) were established in mice to evaluate tumor growth, survival, and immune cell infiltration following treatment with mRNA-LNP or control agents. Safety was assessed in human IFNAR transgenic mice. In vitro experiments demonstrated successful transfection and bioactive fusion protein expression by mRNA-LNP, with transfected supernatants showing specific GPC3 binding and interferon-stimulated gene (ISG) induction. In vivo studies revealed that GPC-3/IFN-α mRNA-LNP significantly inhibited tumor growth, prolonged median survival, and increased intratumoral CD8⁺ T cell and NK cell infiltration compared to controls, with favorable safety profiles. Combination therapy with PD-1 antibody (PD-1 Ab) exerted synergistic antitumor effects, primarily dependent on CD8⁺ T cell infiltration. Safety evaluations in human IFNAR transgenic mice showed good tolerability at single doses of 1-10 mpk, with transient changes in select biomarkers. Repeated dosing (6 or 10 mpk) identified a maximum tolerated dose (MTD) of 6 mpk, at least 40-fold higher than the minimal effective dose (MED, 0.15 mpk). mRNA-LNP-mediated delivery of IFN-α-anti-GPC3 fusion protein achieves targeted in situ hepatic expression, significantly enhancing antitumor activity with a broad therapeutic window. This strategy offers a novel approach for precision immunotherapy in HCC, holding substantial potential for clinical translation.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery of monoclonal antibodies to the brain: the impact of nanocarrier structure.","authors":"Laura Pineiro-Alonso, Inés Rubio-Prego, Ana M López-Estévez, Pablo Garrido-Gil, Rita Valenzuela, José L Labandeira-García, Pablo Aguiar, Ana I Rodríguez-Pérez, María J Alonso","doi":"10.1007/s13346-025-01957-y","DOIUrl":"https://doi.org/10.1007/s13346-025-01957-y","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) are promising therapeutic agents for neurological disorders due to their high specificity. However, their clinical application is significantly hindered by their poor transport across the blood-brain barrier (BBB) and their limited diffusion within the brain parenchyma. While significant efforts have been oriented to tackle the first barrier, the challenge of efficient brain diffusion remains largely underexplored. To address this, we have developed and evaluated two structurally distinct nanosystems for mAb delivery to the brain: PEGylated polyglutamic acid nanocapsules (PGA-PEG NCs) and PGAC14-based nanoassemblies (PGAC14 NAs). Both formulations encapsulated efficiently the model mAb bevacizumab (BVZ) while they exhibited different physicochemical properties. Namely, PGA-PEG NCs displayed a size of 80 nm and a neutral zeta potential, whereas PGAC14 NAs featured an ultra-small size of 40 nm and a negative surface charge. After assessing their diffusion capacity using immunofluorescence, we concluded that PGAC14 NAs exhibited the highest brain diffusion together with a favorable neuroinflammatory profile. This was likely driven by their small size and negative charge, along with a selective ability to interact with and deliver BVZ intracellularly to neuronal cells upon intraparenchymal administration. These findings provide key insights into optimizing nanocarrier design for improved mAb delivery to the brain.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a microneedle patch for delivery of mRNA-lipid nanoparticles.","authors":"Sophia H Sakers, B Pradeep K Reddy, Gianna Fiduccia, Katherine E Byrne, Ingrid Stén, Julie Kim, Afsane Radmand, James E Dahlman, Mark R Prausnitz","doi":"10.1007/s13346-025-01964-z","DOIUrl":"https://doi.org/10.1007/s13346-025-01964-z","url":null,"abstract":"<p><p>mRNA delivered by microneedle patch (MNP) can enable painless delivery, reduced need for healthcare expertise, and improved thermostability. In this study, we investigated formulation and manufacturing approaches for developing MNPs that deliver mRNA-loaded lipid nanoparticles (LNPs) encoding luciferase as a reporter protein during MNP fabrication and storage, including mRNA-LNP concentration, formulation, pH, excipients, and backing material. MNPs were assessed for mRNA-LNP size, encapsulation efficiency, and protein expression in vitro and in vivo. MNPs fabricated with mRNA-LNPs initially prepared at a higher concentration yielded superior expression compared to mRNA-LNP concentration by centrifugation or tangential flow filtration. Acidic pH during MNP manufacturing enabled greater expression in vitro. However, no such correlation was observed in vivo. Polyvinyl alcohol (PVA) best stabilized mRNA-LNPs during the MNP manufacturing process amongst the tested polymers. Incorporating sugars in MNPs did not further improve stability. Low temperature drying (5 °C) preserved mRNA functionality better compared to drying at 25 °C and 40 °C. Though there was significant activity loss initially (87% loss in 2 days at 40 °C), mRNA expression was stabilized for extended subsequent periods even at accelerated conditions (10% additional loss after 28 days at 40 °C). Our systematic approach identified key parameters for successful formulation and manufacturing approaches to incorporate mRNA-LNPs into MNPs, which could expand access to mRNA-based medical interventions.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical delivery of siRNA to psoriatic skin model using high molecular weight chitosan derivatives: In vitro and in vivo studies.","authors":"André Miguel Martinez Junior, Thalles Fernando Rocha Ruiz, Patrícia Simone Leite Vilamaior, Vera Aparecida de Oliveira Tiera, Sebastião Roberto Taboga, Marcio José Tiera","doi":"10.1007/s13346-025-01800-4","DOIUrl":"10.1007/s13346-025-01800-4","url":null,"abstract":"<p><p>Psoriasis is a chronic inflammatory skin disease that, like other immune-mediated conditions, may benefit from small interfering RNA (siRNA)-based therapies, which are emerging as a promising alternative by addressing several limitations of current treatments. In this study, topical formulations of chitosan-based vectors were developed to deliver siRNA targeting tumor necrosis factor alpha (TNFα) to inflamed skin. Grafting diisopropylethylamine (DIPEA) and polyethylene glycol (PEG) onto the chitosan backbone enhanced siRNA delivery efficiency under physiological conditions, forming robust polymeric vectors with high structural and colloidal stability. These vectors provided siRNA protection against RNAse degradation and oxidative damage. Additionally, the chitosan derivatives displayed lysozyme-mediated biodegradability comparable to native chitosan, while PEG was released in response to reductive environments, supporting controlled vector disassembly. The PEGylated DIPEA-chitosan/siRNA polyplexes demonstrated positive zeta potentials (up to + 11 mV), particle sizes of 100-200 nm, and very low cytotoxicity in keratinocyte and fibroblast cell lines. In vitro, the polyplexes achieved TNFα knockdown levels (65%) in RAW macrophages, comparable to those obtained with Lipofectamine™. Topical formulations showed enhanced interaction of vectors with skin models (Strat-M^® and porcine ear skin) compared to naked siRNA. Furthermore, in vivo studies indicated that hair follicles were a key route for polyplexes to penetrate deeper skin layers. A rodent model of psoriasis induced by imiquimod was treated topically with these vectors, resulting in approximately a 50% reduction in TNFα levels at inflammation sites, decreased immune cell infiltration, and preservation of epidermal structure. These findings collectively underscore the potential of DIPEA-chitosan-based vectors for topical siRNA-based therapies.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3199-3225"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serotransferrin enhances transferrin receptor-mediated brain uptake of antibodies.","authors":"Jamie I Morrison, Nicole G Metzendorf, Jielu Liu, Greta Hultqvist","doi":"10.1007/s13346-025-01811-1","DOIUrl":"10.1007/s13346-025-01811-1","url":null,"abstract":"<p><p>The propensity of antibody-based therapies to systemically enter the brain interstitium and ameliorate pathology associated with numerous neurological maladies is precluded by the presence of the blood-brain barrier (BBB). Through distinct mechanisms, the BBB has evolved to regulate transport of essential ions, minerals, certain peptides and cells between the blood and the brain, but very restrictive otherwise. Hijacking receptor-mediated transport pathways of the BBB has proved fruitful in developing \"Trojan Horse\" therapeutic approaches to deliver antibody-based therapies to the brain milieu. The transferrin receptor (TfR)-mediated transcytosis pathway (RMT) is one such example where large recombinant molecules have been designed to bind to the TfR, which in turn activates the RMT pathway, resulting in delivery across the BBB into the brain milieu. Based on these findings, we here investigated whether the addition of serotransferrin could trigger the endogenous TfR-mediated RMT pathway and hence be used to enhance the uptake of TfR binding antibodies. By using an in vitro model of a mouse BBB we could test whether co-administration of mouse serotransferrin with mouse and human-based monoclonal antibodies enhanced brain uptake. In all cases tested, no matter if the monoclonal antibodies were designed to bind the TfR in a monovalent, partially monovalent/bivalent or entirely bivalent fashion, with high or low affinity or avidity, the addition of mouse serotransferrin significantly improved transport across the artificial BBB. This was also true for TfR binding antibodies that on their own passes the BBB poorly. These results were subsequently confirmed using a human in vitro BBB model, along with human serotransferrin and human TfR-binding antibody. To corroborate the in vitro results further, we conducted two pilot in vivo brain uptake study in wildtype mice, by intravenously co-administering a monoclonal TfR-binding antibody in the presence or absence of mouse serotransferrin as a proof-of-concept. In a similar outcome to the in vitro studies, we observed a significant almost two-fold increase in uptake of two different TfR binding antibodies in the brain when it was co-administered with mouse serotransferrin. These findings show for the first time that serotransferrin supplementation can significantly improve the ability of TfR-binding antibodies to traverse the BBB, which provides a realistic therapeutic opportunity for improving the delivery of therapeutic antibodies to the brain.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3321-3337"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-assembly of multi-arm star PEG containing TXA9 into nanoparticle for the efficient chemotherapy of NSCLC.","authors":"Qilong Wang, Zhe Liu, Jiale Yao, Haosheng Xie, Zhihui Liu, Jianxiu Zhai, Sikai Li, Jia Ming Zhang, Na Han, Jun Yin","doi":"10.1007/s13346-025-01793-0","DOIUrl":"10.1007/s13346-025-01793-0","url":null,"abstract":"<p><p>TXA9, a cardiac glycoside isolated from the root of Streptocaulon juventas (Lour.) Merr., with better therapeutic effect in vitro on non-small cell lung cancer (NSCLC) than cisplatin and has no toxic side effects on the body. However, poor water solubility and rapid metabolism limited its clinical application. Multi-arm star PEG have many advantages over linear PEG, such as high drug loading due to more terminals and better anti-hemodilution ability, which have become popular carriers for drug delivery. In this study, to improve the efficacy of TXA9, 6/8armPEG_n-Glycine Carbamate (Gly) (n = 10, 20, and 40 kDa) were used as carriers to prepare star PEG-TXA9 conjugates. The particle size and zeta potential of six prodrug NPs for effective tumor targeting, with suitable drug loading, and good water solubility. Compared with free TXA9, 6/8APG_n-T NPs had more significant anti-tumor effects in vitro. Since the multi-arm star PEG formed an \"umbrella\" structure on the surface of NPs, the 8APG_40k-T NPs with the best pharmacokinetic properties increased half-life of TXA9 about 60 times in vivo. In addition, the arm numbers and molecular weight of multi-arm star PEGs significantly influenced the in vivo destiny of prodrugs. In vivo experiments showed that the same dose of 8APG_40k-T NPs increased the tumor inhibition rate about 3.56 or 1.22 times compared with TXA9 or cisplatin, and had good biocompatibility. This study provides a simple but effective strategy to solve the challenges caused by the poor water solubility and short half-life of TXA9 for developing the TXA9 as a safe and effective drug against NSCLC.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3119-3136"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Injectable nanocomposite hydrogels for targeted intervention in cancer, wound healing, and bone and myocardial tissue engineering.","authors":"Ana Rita Pereira, Patrícia C Pires, Huma Hameed, Daniela Lopes, Joana Lopes, Inês Sousa-Oliveira, Soraya Babaie, Priscila Mazzola, Francisco Veiga, Ana Cláudia Paiva-Santos","doi":"10.1007/s13346-025-01864-2","DOIUrl":"10.1007/s13346-025-01864-2","url":null,"abstract":"<p><p>Despite current medicine's fast-paced advances, many acute and chronic illnesses still lack truly effective and safe therapies. Cancer treatments often lead to off-target healthy tissue damage and poor therapeutic outcomes, wound standard treatments generally demonstrate poor healing efficacy and increased susceptibility to infection, and bone tissue engineering and myocardial tissue engineering can result in immunological rejection and limited availability. To tackle these issues, injectable hydrogels have emerged, and through the incorporation of nanoparticles, nanocomposite hydrogels have appeared as versatile platforms, offering improved biocompatibility, mechanical strength, stability, and precise controlled drug release, as well as targeted delivery with increased drug retention at the site of action, reducing systemic drug distribution to non-target sites. With the ability to deliver a diverse range of therapeutic entities, including low molecular weight drugs, proteins, antibodies, and even isolated cells, injectable nanocomposite hydrogels have revolutionized current therapies, working as multifunctional platforms capable of improving efficacy and safety in cancer treatment, including in chemotherapy, immunotherapy, photothermal therapy, magnetic hyperthermia, photodynamic therapy, chemodynamic therapy, radiotherapy, molecularly targeted therapy, and after tumor surgical removal, and in general, chronic diabetic or tumor-induced wound healing, as well as in bone tissue engineering and myocardial tissue engineering. This review provides a thorough summary and critical insight of current advances on injectable nanocomposite hydrogels as an innovative approach that could bring substantial contributions to biomedical research and clinical practice, with a focus on their applications in cancer therapy, wound healing management, and tissue engineering.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2994-3077"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microneedle patches: the next frontier in cardiovascular care.","authors":"Simran Deep Kaur, Shivanshu Choudhary, Santimoy Sen, Deepak B Pemmaraju, Sachin Kumar Singh, Deepak N Kapoor","doi":"10.1007/s13346-025-01802-2","DOIUrl":"10.1007/s13346-025-01802-2","url":null,"abstract":"<p><p>Myocardial infarction is a condition where the heart muscle is damaged due to clogged coronary arteries. There are limited treatment options for treating myocardial infarction. Microneedle patches have recently become popular as a possibly viable therapy for myocardial. By adhering to the surface of the heart, these microneedle patches provide mechanical support, regenerative medicines, or cells directly to the injured tissue allowing for targeted treatment. These microneedle patches resolve the drawbacks of systemic therapy by facilitating targeted administration and integration with the goal of restoring damaged heart function. Recent advances in fabrication methods and current perspectives on the therapeutic advantages of cardiac microneedles patches used in the treatment of myocardial infarction are summarized in this review. Although the data is less in this area this review provides an avenue for the formulation scientist working in biomedical science to develop such microneedle patches for clinical applications in cardiology.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2951-2966"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A framework for conducting clinical trials involving 3D printing of medicines at the point-of-care.","authors":"Carlos Javier Parramon-Teixido, Lucía Rodríguez-Pombo, Abdul W Basit, Anna Worsley, Carme Cañete-Ramírez, Carmen Alvarez-Lorenzo, Maria Josep Cabañas-Poy, Alvaro Goyanes","doi":"10.1007/s13346-025-01868-y","DOIUrl":"10.1007/s13346-025-01868-y","url":null,"abstract":"<p><p>The integration of 3D printing (3DP) technologies into personalized medicine manufacture at the point-of-care is garnering significant interest due to its potential to create tailored drug products with precise dosages and other unique attributes. Both preclinical and clinical studies have demonstrated promising outcomes, including pharmacokinetic bioequivalence, improved patient acceptability, enhanced adherence, and the ability to produce consistent, reproducible dosage forms with accurate drug distribution. Some compounding pharmacies around the world are already incorporating 3DP into standard practice for simpler therapeutic treatments. However, further clinical evaluation is required for more complex treatments, such as multi-drug polypills. Conducting clinical trials involving 3DP technologies presents several challenges, including navigating evolving regulatory frameworks, addressing ethical and legal concerns, and complying with new point-of-care manufacturing guidelines. Although regulatory agencies are beginning to adapt their policies to accommodate 3DP, the absence of a comprehensive framework still creates uncertainty for pharmacists and healthcare providers. This article explores the planning and execution of clinical trials involving 3D printed medicines, with a focus on regulatory barriers, patient recruitment, compliance, and the integration of specialized equipment and expertise. It also discusses the implementation of 3DP for personalized drug manufacturing within hospital settings and offers guidance for obtaining clinical trial approval from the Spanish Agency for Medicine and Health Products (AEMPS). By providing these insights and recommendations, this article aims to support international harmonization and facilitate the adoption of 3DP technologies in clinical trials globally.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3078-3097"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rifamycin SV in situ gelling formulation for the treatment of pouchitis.","authors":"Katia Mangano, Cinzia Quatrocchi, Katia Ajello, Stefania Pagani, Gordon Alton, Luigi Longo, Mara Gerloni","doi":"10.1007/s13346-025-01808-w","DOIUrl":"10.1007/s13346-025-01808-w","url":null,"abstract":"<p><p>Procto-colectomy with an ileal pouch anal anastomosis is performed in Ulcerative Colitis patients as a potential curative surgical option. However, in many patients a non-specific inflammation of the ileal reservoir can occur, named pouchitis. Some patients further develop a chronic antibiotic-resistant disease. Rifaximin, an oral, broad-spectrum antibiotic has been shown to have efficacy for some patients. In the present study CB0125, a novel Rifamycin SV in situ gelling formulation, was developed as a potential pouchitis therapy. This mixture undergoes sol to gel transition under physiological pH and temperature upon administration to the target organ by enema. The in vivo efficacy of the in situ gel was performed using dextran sodium sulphate-induced colitis model in C57/Bl6 mice. The clinical parameters such as body weight changes, rectal bleeding and stool consistency were compared to mesalamine (positive control). In addition, a histopathological investigation was conducted to assess severity of mucosal damage and inflammation infiltrate. CB0125 was well tolerated and there was a significant reduction in disease activity, improved colon weight to length ratio, and improved histology score for the CB-01-25 in situ gel group compared to placebo gel. In addition, CB0125 was superior to mesalamine and to rifamycin SV dissolved in water. We propose that the rifamycin SV in situ gel may provide a longer duration of exposure of this dual acting antibiotic / anti-inflammatory drug at the site of the damaged intestinal mucosa resulting in a superior combined effect, relative to rifamycin SV dissolved in water, for the treatment of pouchitis.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3296-3306"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}