Drug Delivery and Translational Research最新文献

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Microfluidic fabrication of pectin-coated liposomes for drug delivery.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-02-22 DOI: 10.1007/s13346-025-01812-0
Anitta Lutta, Qian Liu, Gabriel Kristian Pedersen, Mingdong Dong, Holger Grohganz, Line Hagner Nielsen, Signe Tandrup Schmidt
{"title":"Microfluidic fabrication of pectin-coated liposomes for drug delivery.","authors":"Anitta Lutta, Qian Liu, Gabriel Kristian Pedersen, Mingdong Dong, Holger Grohganz, Line Hagner Nielsen, Signe Tandrup Schmidt","doi":"10.1007/s13346-025-01812-0","DOIUrl":"https://doi.org/10.1007/s13346-025-01812-0","url":null,"abstract":"<p><p>Polymer coating of nanoparticulate drug delivery systems may enhance the efficacy of oral delivery. Cationic liposomes were coated with pectin biopolymers using microfluidics, with systematic variation of process parameters to optimize pectin-coated liposome fabrication. A pectin/liposome weight ratio of 0.7 and a microfluidic flow rate ratio of 2:1 pectin:liposome were found to be optimal. The resulting formulations displayed particle sizes at least threefold the size of uncoated liposomes, while the surface charge shifted to a highly negative value, indicating full pectin coating of the particles. Further microscopic characterization of the pectin-coated liposomes revealed that the pectins formed a polymeric network within which the liposomes were dispersed or attached. Stability studies revealed that pectin-coated liposomes remained stable during storage, with no displacement of the coating. We determined that microfluidics is a robust method for preparing pectin-coated liposomes, despite the structural differences between the pectins, geometry of the microchip used, and pectin/liposome concentration. Ultimately, the use of microfluidics in formulation development could be highly beneficial, as the process parameters can be easily modified and the process is easily scalable and inexpensive. Additionally, pectins can offer protective properties to the liposomes particularly during oral drug delivery.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476348","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}
引用次数: 0
Skin penetration enhancers: Mechanistic understanding and their selection for formulation and design.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-02-21 DOI: 10.1007/s13346-025-01809-9
Yee Shan Sim, Li Ching Wong, Soo Chin Yeoh, Abdulsalam Almashhadani, Bilal Harieth Alrimawi, Choon Fu Goh
{"title":"Skin penetration enhancers: Mechanistic understanding and their selection for formulation and design.","authors":"Yee Shan Sim, Li Ching Wong, Soo Chin Yeoh, Abdulsalam Almashhadani, Bilal Harieth Alrimawi, Choon Fu Goh","doi":"10.1007/s13346-025-01809-9","DOIUrl":"https://doi.org/10.1007/s13346-025-01809-9","url":null,"abstract":"<p><p>The skin functions as a formidable barrier, particularly the stratum corneum, effectively restricting the penetration of most substances, including therapeutic agents. To circumvent this barrier, skin penetration enhancers (SPEs) are frequently employed to transiently increase skin permeability, facilitating drug absorption without causing irritation or damage. Despite advancements in dermal formulation development, a deeper understanding of the fundamental science underpinning drug delivery via SPEs remains essential. This review delivers a critical update on conventional SPEs, exploring their mechanisms in promoting drug permeation across the skin. In addition to offering an overview of percutaneous drug delivery, we examine the prevailing theories on how SPEs enhance drug transport. Furthermore, we address the intricate interplay between SPEs, drugs and the skin, providing valuable insights into how the molecular properties and permeation behaviours of SPEs influence their efficacy. This comprehensive review aims to support the ongoing development of optimised drug delivery systems for dermal applications by elucidating the complexities and challenges involved in using SPEs effectively.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467297","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}
引用次数: 0
Application of platelet-rich plasma lysate combined with hyaluronic acid microneedles for the treatment of alopecia. 应用富血小板血浆溶胞物结合透明质酸微针治疗脱发。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-02-21 DOI: 10.1007/s13346-025-01816-w
Zhengxin Suo, Yingcan Xu, Along Zhang, Ye Cao, Jiaxin Liu, Hong Wang, Rui Zhong
{"title":"Application of platelet-rich plasma lysate combined with hyaluronic acid microneedles for the treatment of alopecia.","authors":"Zhengxin Suo, Yingcan Xu, Along Zhang, Ye Cao, Jiaxin Liu, Hong Wang, Rui Zhong","doi":"10.1007/s13346-025-01816-w","DOIUrl":"https://doi.org/10.1007/s13346-025-01816-w","url":null,"abstract":"<p><p>Androgenetic alopecia (AGA) continues to pose a significant challenge due to the paucity of effective therapeutic options. Upon lysis, platelet-rich plasma (PRP) releases numerous growth factors (GFs), which facilitate tissue reconstruction and hair regeneration. However, concerns such as infection, bleeding, local erythema, and patient anxiety associated with injections have substantially diminished patient acceptance. To address these issues, we developed a microneedle (MN) system loaded with PRP lysate (PL), termed PL-MN, designed to deliver GFs transdermal to sites of hair loss without inducing significant discomfort. The PL-MN not only exhibits a well-defined needle structure but also demonstrates excellent in vivo penetration and external transdermal efficacy. Upon skin penetration, the needle matrix rapidly dissolves, releasing GFs directly to the target site. In animal tests, the PL-MN shows synergistic effects by orchestrating an upregulation in the expression of Ki67 and CD31, which collectively foster cell proliferation and migration, thereby facilitating the expedited progression of hair follicles (HFs) into the anagen phase and promoting peripheral angiogenesis. Compared with minoxidil, the first-line clinical drug for treating AGA (administered once per day, 20 times in total), the PL-loaded MN could induce hair regeneration in mice with a lower frequency of administration (once every 3 days, 5 times in total). Consequently, such a safe and GFs-releasing MNs patch shows great potential for clinical AGA treatment.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467294","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}
引用次数: 0
Serotransferrin enhances transferrin receptor-mediated brain uptake of antibodies.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-02-19 DOI: 10.1007/s13346-025-01811-1
Jamie I Morrison, Nicole G Metzendorf, Jielu Liu, Greta Hultqvist
{"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":"https://doi.org/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":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mixed dry reverse micelles: potential carriers for oral protein delivery via SEDDS.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-02-18 DOI: 10.1007/s13346-025-01810-2
Fabrizio Ricci, Sera Lindner, Simona Summonte, René Holm, Dajun Sun, Nathaniel Washburn, Cecilia Bohns Michalowski, Giustino Di Pretoro, Andreas Bernkop-Schnürch
{"title":"Mixed dry reverse micelles: potential carriers for oral protein delivery via SEDDS.","authors":"Fabrizio Ricci, Sera Lindner, Simona Summonte, René Holm, Dajun Sun, Nathaniel Washburn, Cecilia Bohns Michalowski, Giustino Di Pretoro, Andreas Bernkop-Schnürch","doi":"10.1007/s13346-025-01810-2","DOIUrl":"https://doi.org/10.1007/s13346-025-01810-2","url":null,"abstract":"<p><p>The aim of this study was to evaluate the potential of mixed dry reverse micelles (dRMs) to increase the lipophilicity of therapeutic proteins and allow their incorporation into self-emulsifying drug delivery systems (SEDDS). Horseradish peroxidase (HRP) was incorporated in mixed dRMs, forming HRP-dRMs, using soybean phosphatidylcholine (SPC) and sodium docusate (SD) as surfactants. HRP-dRMs were characterized with respect to their distribution coefficient and stability in simulated physiological fluids. Moreover, HRP-dRMs were loaded in SEDDS, which were characterized for their payload, stability, distribution coefficients between the lipophilic phase of SEDDS and release medium and their ability to protect the incorporated protein towards enzymatic degradation in aqueous media containing trypsin and chymotrypsin. The synergistic effect of two surfactants to form dRMs led to a payload of 3% (w/v) for the model protein in a lipophilic phase without the use of organic cosolvents. Moreover, the HRP-dRMs incorporation increased the LogD <sub>n-octanol/water</sub> value of HRP from - 3.36 to 3.10. This increment in lipophilicity provided a higher retention of the protein within the oily droplets, and correled with enzymatic degradation studies, where > 95% of the incorporated protein remained intact. This study provided first evidence for unprecedented amount of a model protein of high molecular weight loaded in SEDDS through dRMs incorporation as a possible tool for their oral delivery, with a 15-fold increment compared to the previously achieved results.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448531","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}
引用次数: 0
Nanoscale strategies: doxorubicin resistance challenges and enhancing cancer therapy with advanced nanotechnological approaches.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-02-15 DOI: 10.1007/s13346-025-01790-3
Jian Xin Lim, Yoke Keong Yong, Firli Rahmah Primula Dewi, Siok Yee Chan, Vuanghao Lim
{"title":"Nanoscale strategies: doxorubicin resistance challenges and enhancing cancer therapy with advanced nanotechnological approaches.","authors":"Jian Xin Lim, Yoke Keong Yong, Firli Rahmah Primula Dewi, Siok Yee Chan, Vuanghao Lim","doi":"10.1007/s13346-025-01790-3","DOIUrl":"https://doi.org/10.1007/s13346-025-01790-3","url":null,"abstract":"<p><p>Doxorubicin (DOX), an anthracycline, is widely used in cancer treatment by interfering RNA and DNA synthesis. Its broad antitumour spectrum makes it an effective therapy for a wide array of cancers. However, the prevailing drug-resistant cancer has proven to be a significant drawback to the success of the conventional chemotherapy regime and DOX has been identified as a major hurdle. Furthermore, the clinical application of DOX has been limited by rapid breakdown, increased toxicity, and decreased half-time life, highlighting an urgent need for more innovative delivery methods. Although advancements have been made, achieving a complete cure for cancer remains elusive. The development of nanoparticles offers a promising avenue for the precise delivery of DOX into the tumour microenvironment, aiming to increase the drug concentration at the target site while reducing side effects. Despite the good aspects of this technology, the classical nanoparticles struggle with issues such as premature drug leakage, low bioavailability, and insufficient penetration into tumours due to an inadequate enhanced permeability and retention (EPR) effect. Recent advancements have focused on creating stimuli-responsive nanoparticles and employing various chemosensitisers, including natural compounds and nucleic acids, fortifying the efficacy of DOX against resistant cancers. The efforts to refine nanoparticle targeting precision to improve DOX delivery are reviewed. This includes using receptor-mediated endocytosis systems to maximise the internalisation of drugs. The potential benefits and drawbacks of these novel techniques constitute significant areas of ongoing study, pointing to a promising path forward in addressing the challenges posed by drug-resistant cancers.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425113","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}
引用次数: 0
Bridging membrane fluidity studies with a predictive model of drug encapsulation to address industrial challenges of liposomal injectables manufacturing.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-02-15 DOI: 10.1007/s13346-025-01807-x
Mariana Biscaia-Caleiras, Nuno Fonseca, Ana Sofia Lourenço, António Nunes, Abel Ferreira, João Nuno Moreira, Sérgio Simões
{"title":"Bridging membrane fluidity studies with a predictive model of drug encapsulation to address industrial challenges of liposomal injectables manufacturing.","authors":"Mariana Biscaia-Caleiras, Nuno Fonseca, Ana Sofia Lourenço, António Nunes, Abel Ferreira, João Nuno Moreira, Sérgio Simões","doi":"10.1007/s13346-025-01807-x","DOIUrl":"https://doi.org/10.1007/s13346-025-01807-x","url":null,"abstract":"<p><p>Industrial manufacturing of liposomal drugs, often involves high-temperature processes, resulting in increased energy consumption, prolonged process times, and elevated costs, while posing risks of phospholipid and drug degradation. The current study addresses these challenges by exploring remote loading of doxorubicin into liposomes, at temperatures below the phase transition temperature (PTT) of the primary phospholipid (DSPC, 55 °C). Drug loading efficiencies exceeding 90% at 45 °C were achieved, while efficiencies dropped significantly (6-fold and 23-fold) at 37 °C and 25 °C, respectively. This prompted the hypothesis that efficient drug loading might be attained below the PTT, when a minimal threshold for liposomal membrane fluidity is overcome. Using design of experiments (DoE), key factors influencing fluidity were identified: temperature, cholesterol content and surface tension (dependent on the isotonic agent). A full factorial DoE confirmed that membrane fluidity increased with lower surface tension, and high cholesterol content. A predictive model was also generated establishing a correlation between drug loading efficiency, membrane fluidity, and drug partitioning coefficient (logP). This model revealed that doxorubicin (logP = 1.5) requires a fluidity threshold of 4.41 for efficient loading (≥ 90%), whereas daunorubicin (logP = 2.32) needs a lower threshold of 3.85, suggesting that drugs with higher logP values demand lower fluidity thresholds for effective loading. The model's applicability was validated across various lipid formulations, enabling effective drug loading at temperatures as low as 25 °C, potentially reducing degradation risks and energy costs. Overall, these findings highlight the relevance of liposomal membrane fluidity studies as a potential tool for enabling more effective industrial processes.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425111","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}
引用次数: 0
Development of buspirone hydrochloride-loaded long-acting microneedles for management of anxiety disorders.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-02-14 DOI: 10.1007/s13346-025-01803-1
Tanvi Karve, Nisha Shrestha, Thomas Kipping, Ajay K Banga
{"title":"Development of buspirone hydrochloride-loaded long-acting microneedles for management of anxiety disorders.","authors":"Tanvi Karve, Nisha Shrestha, Thomas Kipping, Ajay K Banga","doi":"10.1007/s13346-025-01803-1","DOIUrl":"https://doi.org/10.1007/s13346-025-01803-1","url":null,"abstract":"<p><p>Buspirone hydrochloride (BSP) is an anxiolytic agent approved for the management of anxiety disorders. The current US-FDA approved medications of BSP are administered via the oral route, which is linked to several disadvantages such as low oral bioavailability and low half-life necessitating multiple daily doses. For chronic diseases such as anxiety disorders, where long-term or lifelong management is often required, these factors impact patient compliance and treatment adherence. The present study offers an alternative treatment approach by investigating the feasibility of sustained transdermal delivery of BSP via long-acting microneedles (MNs). Needle-tip-loaded MNs were fabricated via micro-molding technique using various grades of poly-vinyl alcohol (PVA) namely 4-88, 8-88, 18-88, and 26-88. These MNs were compared using characterization techniques such as Parafilm<sup>®</sup> insertion testing, scanning electron microscopy (SEM), confocal microscopy, Fourier transform infrared spectroscopy (FTIR), and histological evaluation of MNs-treated human skin. The effect of different grades of PVA on the structural and mechanical properties of the fabricated MNs was evaluated. Further, in vitro release and permeation tests were conducted to assess the drug release patterns and transdermal delivery across dermatomed human skin over 7-day study periods. The highest release (5507.37 ± 456.88 µg/cm<sup>2</sup>) and delivery (4705.42 ± 634.57 µg/cm<sup>2</sup>) were observed from PVA 4-88, with significant differences among the PVA grades based on their properties. Notably, all four types of the fabricated PVA MNs crossed the daily and weekly therapeutic targets for the systemic delivery of BSP. Overall, this study established the feasibility of sustained delivery of BSP across the skin using PVA MNs for the management of anxiety disorders.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425112","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}
引用次数: 0
A rifamycin SV in situ gelling formulation for the treatment of pouchitis.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-02-13 DOI: 10.1007/s13346-025-01808-w
Katia Mangano, Cinzia Quatrocchi, Katia Ajello, Stefania Pagani, Gordon Alton, Luigi Longo, Mara Gerloni
{"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":"https://doi.org/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":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-13","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}
引用次数: 0
Nano-spanlastics-loaded dissolving microneedle patches for ketotifen fumarate: advanced strategies for allergic conjunctivitis treatment and molecular insights. 富马酸酮替芬的纳米跨膜载体可溶微针贴片:过敏性结膜炎治疗的先进策略和分子研究。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-02-11 DOI: 10.1007/s13346-025-01796-x
Sammar Fathy Elhabal, Mohamed El-Nabarawi, Mohamed Fathi Mohamed Elrefai, Mahmoud H Teaima, Mai S Shoela, Gehad M Khamis, Ahmed Mohsen Faheem, Nada Ahmed Kholeif, Mahmoud Tarek Sanad
{"title":"Nano-spanlastics-loaded dissolving microneedle patches for ketotifen fumarate: advanced strategies for allergic conjunctivitis treatment and molecular insights.","authors":"Sammar Fathy Elhabal, Mohamed El-Nabarawi, Mohamed Fathi Mohamed Elrefai, Mahmoud H Teaima, Mai S Shoela, Gehad M Khamis, Ahmed Mohsen Faheem, Nada Ahmed Kholeif, Mahmoud Tarek Sanad","doi":"10.1007/s13346-025-01796-x","DOIUrl":"https://doi.org/10.1007/s13346-025-01796-x","url":null,"abstract":"<p><p>Allergic conjunctivitis (AC) is the most common inflammatory disease affecting the eye's ocular surface, lid, conjunctiva, and cornea. However, effective ocular drug delivery remains challenging due to physiological barriers such as the corneal barrier. Ketotifen (KF), a widely used antihistamine and mast cell stabilizer, for treating AC and atopic asthma but belongs to the Biopharmaceutical Classification System (BCS II) have poor solubility. This study developed a multiple strategies approach for the first time, utilizing the spanlastics nano-vesicular carriers' system (SP) containing KF using an ethanol injection method. The optimized KF-SP exhibited the smallest particle size, largest zeta-potential and entrapment efficiency ∼232.5 ± 1.9 nm, -28 ± 0.51 and 73 ± 0.02%, respectively were further incorporated into PVA/PVP polymeric dissolving microneedles (MNs) by using a micromolding technique. Scanning electron microscopy (SEM) analysis confirmed well-defined tips and morphology, and in vitro studies showed a controlled 93% cumulative release over 72 h, with a zero-order kinetic release profile, providing stable therapeutic levels. Pharmacodynamic evaluation using the Ovalbumin/Aluminium hydroxide-induced AC model demonstrated significant reductions in IgE, TNF-α, and IL-6 levels by 68.7%, 71.3%, and 67.6%, respectively, while TGF-β and IL-10 levels increased by 70.1% and 62.7% using ELISA (Enzyme-Linked Immunosorbent Assay). Gene expression analysis (IGF-1, Annexin A1, and Bcl2) further supported the therapeutic potential of this system. In this study, we proved the topical application of the multiple strategies approach KF-SP loaded PVA/PVP MNs patch offers a targeted, sustained release treatment for AC, with promising implications for prolonged ocular therapy.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398633","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}
引用次数: 0
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