International Journal of Pharmaceutics: X最新文献

{"title":"A single oral administration of resveratrol cocrystals enables potent antisepsis therapy via interfering neutrophil extracellular traps formation","authors":"Juexian Wei ,&nbsp;Muhammad Inam ,&nbsp;Hengzong Mo ,&nbsp;Jiayu Huang ,&nbsp;Hongyu Zhao ,&nbsp;Aijia Zhong ,&nbsp;Xiaoyan Tang ,&nbsp;Ehua Deng ,&nbsp;Chuanshan Xu ,&nbsp;Xiaohui Chen ,&nbsp;Haifeng Mao ,&nbsp;Wenjie Chen ,&nbsp;Junrong Mo ,&nbsp;Yongcheng Zhu","doi":"10.1016/j.ijpx.2025.100386","DOIUrl":"10.1016/j.ijpx.2025.100386","url":null,"abstract":"<div><div>Sepsis is a life-threatening syndrome characterized by organ dysfunction resulting from host response disorders and is a common complication in patients suffering from clinical trauma, burns, and infections. Resveratrol, a natural polyphenol compound, possesses anti-inflammatory, antiviral, antibacterial, and antifungal properties, as well as cardiovascular and anti-tumor protective effects. However, its therapeutic applications have been limited due to low bioavailability, poor aqueous solubility, and rapid metabolism. To address these limitations, this study focused on the preparation of resveratrol (RES) cocrystal with nicotinamide (NCA) and RES polymorphs through recrystallization for oral application. The identity of the new crystalline forms was confirmed using powder X-ray diffraction (PXRD), Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and single-crystal X-ray diffraction (SCXRD). Physicochemical evaluations revealed that the RES polymorphs and RES-NCA cocrystal exhibited higher solubility and dissolution rates compared to pristine RES. In vitro experiments with LPS-stimulated HL-60 cells demonstrated that the RES-NCA cocrystal effectively inhibited neutrophil extracellular traps (NETs) formation by targeting peptidylarginine deiminase 4 (PADI4) and reducing inflammatory markers. Additionally, in vivo studies using a cecal ligation and puncture (CLP)-induced sepsis model in mice showed that oral administration of the RES-NCA cocrystal significantly reduced NETs formation, organ injury, and mortality. These findings suggest that orally administered RES-NCA cocrystal holds promise as a therapeutic agent for sepsis treatment, offering enhanced solubility and bioavailability, along with potent effects in inhibiting NETs formation and reducing sepsis-induced organ injury.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100386"},"PeriodicalIF":6.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-concentration L-methionine as a potent antioxidant for oxidation resistance and stability enhancement in high-concentration antibody therapeutics","authors":"Xuekun Wang ,&nbsp;Xinyu Zhang ,&nbsp;Jin Xu ,&nbsp;Shuhai Xu ,&nbsp;Keyuan Huang ,&nbsp;Qiaoling Ni ,&nbsp;Xinyi Shen ,&nbsp;Weitao Zhang ,&nbsp;Tao Liu ,&nbsp;Taimin Dong ,&nbsp;Dan Mao ,&nbsp;Chunguang Zheng ,&nbsp;Wei Yu ,&nbsp;Qingcheng Guo ,&nbsp;Zhixin Li ,&nbsp;Jiawei Cao ,&nbsp;Fubo Han ,&nbsp;Lusha Ji ,&nbsp;Weizhu Qian ,&nbsp;Sheng Hou ,&nbsp;Huaizu Guo","doi":"10.1016/j.ijpx.2025.100385","DOIUrl":"10.1016/j.ijpx.2025.100385","url":null,"abstract":"<div><div>The development of high-concentration monoclonal antibody (mAb) formulations for subcutaneous administration is faces critical stability challenges, particularly oxidation and aggregation, which compromise efficacy and safety. While antioxidants are commonly employed, existing studies predominantly focus on low concentrations, leaving the potential of high-concentration antioxidants underexplored. Here, we present the first systematic evaluation of high-concentration L-methionine (L-Met,&gt;20 mM) as a novel antioxidant to address these limitations. Through accelerated stability testing coupled with multi-dimensional analytical techniques, we demonstrated that L-Met at concentrations exceeding 20 mM surpasses conventional antioxidants in mitigating oxidation and aggregation. Synergy with 200 mM trehalose further enhanced stability by reducing oxidative degradation and inhibiting protein aggregation. Comprehensive biophysical analyses confirmed no adverse effects, with some aspects showing improved outcomes in structural integrity, colloidal stability, and thermal behavior. The optimized formulation (25 mM L-Met +200 mM trehalose) also exhibited robust protection against light-induced degradation and broad applicability across therapeutic antibodies. This work pioneers a high-concentration antioxidant strategy, addressing a critical gap in mAb formulation science and offering a translatable solution for stabilizing next-generation high-concentration biologics.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100385"},"PeriodicalIF":6.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MgZnFe-layered double hydroxides as a dual-function platform for enhancing subunit vaccine efficacy in tumor immunotherapy","authors":"Xue Wang ,&nbsp;Lu Liu ,&nbsp;Yingying Chen ,&nbsp;Lirui Jia ,&nbsp;Yongjun Wang ,&nbsp;Wei Jing ,&nbsp;Guangqi Yan","doi":"10.1016/j.ijpx.2025.100384","DOIUrl":"10.1016/j.ijpx.2025.100384","url":null,"abstract":"<div><div>Therapeutic cancer vaccines show promise in immunotherapy but face challenges such as poor antigen delivery, insufficient immune activation, and an immunosuppressive tumor microenvironment, limiting tumor-specific cellular immunity. In this study, we present a dual-function tumor vaccine platform, MgFeZn-Layered double hydroxide (LMFZ), serving as both an antigen delivery system and immune adjuvant to enhance antitumor responses. Loaded with antigens, nanometer-sized LMFZ particles efficiently traffic to lymph nodes, promoting antigen capture by dendritic cells (DCs). LMFZ endosomal escape enables antigen cross-presentation and enhances DC maturation, boosting cytotoxic T lymphocyte proliferation and tumor infiltration. LMFZ also neutralizes tumor acidity, induces M1 polarization of macrophage, and enhances natural killer cell activity via Zn²⁺ supplementation, amplifying antitumor immunity. Following two peritumoral subcutaneous injections, antigen-loaded LMFZ demonstrated significant antitumor efficacy with minimal adverse effects in a mouse model. This highlights the potential of LMFZ vaccine platform for clinical translation and offers an innovative strategy to address the limitations of current therapeutic vaccine-based immunotherapies.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100384"},"PeriodicalIF":6.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of recycling pharmaceutical formulations in laser powder bed fusion 3D printing - the influence of physical phenomena on printing performance","authors":"Wessel Kooijman ,&nbsp;Valerie R. Levine ,&nbsp;Robbert J. Kok ,&nbsp;Jonas Lindh ,&nbsp;Julian Quodbach","doi":"10.1016/j.ijpx.2025.100383","DOIUrl":"10.1016/j.ijpx.2025.100383","url":null,"abstract":"<div><div>Laser powder bed fusion is an attractive technology for 3D printing objects in a powder bed and has been explored for printing pharmaceutical dosage forms, such as tablets. Recycling of non-sintered residual powder is not well understood, but is critical to prevent economic losses and improve the sustainability of this technique. We investigated the recyclability of three pharmaceutical formulations in the context of laser powder bed fusion of tablets. Three formulations consisting of common pharmaceutical polymers and the model drug indomethacin have been investigated up to ten print cycles. For each print cycle, powder and tablet samples were collected and analyzed for ageing phenomena. Results showed that polyvinyl alcohol and methacrylic acid-ethyl acrylate copolymer-based formulations were recyclable without changes in critical quality attributes of printed dosage forms for 5 and 9 cycles, respectively. A copovidone-based formulation showed a gradual increase in particle size over 10 cycles, resulting in a gradual decrease in tablet weight. This formulation was considered non-recyclable under the conditions evaluated in this work. The observed ageing phenomena were mainly related to changes in particle size, powder cohesion, and glass transition temperature. It is shown that considering powder ageing during formulation development is critical for optimal print performance and further development of laser powder bed fusion for pharmaceutical applications.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100383"},"PeriodicalIF":6.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 potential nano-based delivery system combining Colchicine-loaded lipid nanocapsules and BIOT-NFL-peptide to target glioblastoma","authors":"H. Alnemeh-Al Ali ,&nbsp;J. Bejaud ,&nbsp;N. Lautram ,&nbsp;A. Dupont ,&nbsp;J. Eyer","doi":"10.1016/j.ijpx.2025.100382","DOIUrl":"10.1016/j.ijpx.2025.100382","url":null,"abstract":"<div><div>Peptide conjugated-nanodrug is one of the most studied new treatment options in the field of cancer, including glioblastoma (GBM). This tumour, GBM, is a difficult to treat brain tumour mainly due to its location and the complexity of targeting tumour cells. A promising GBM-targeting peptide (NFL-TBS.40–63) is a cell penetrating peptide (CPP) that has previously demonstrated selectivity against GBM cells and also a capacity to damage their microtubule network at appropriate concentrations. Here, a potential nano-based delivery system was developed by coupling the biotinylated-NFL-peptide (BIOT-NFL) with lipid nanocapsules (LNCs) loaded with Colchicine (Col), an anti-microtubule agent with potent anticancer activity. The effect of BIOT-NFL and free Colchicine was first evaluated on GBM cells. Colchicine was then loaded in lipid nanocapsules (Col-loaded LNCs) and the obtained nanocapsules were characterized for particle size, morphology, encapsulation efficiency and <em>in vitro</em> release, and then coupled with the BIOT-NFL-peptide. Interestingly, a potential nanosystem composed of peptide-nanofibers (formed from BIOT-NFL) decorated with Col-LNCs was observed by electron microscopic examination. Finally, the effects of this BIOT-NFL coupled to Col-LNCs were evaluated <em>in vitro</em> on GBM cells. This new nanosystem may offer a promising strategy for GBM targeted therapy.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100382"},"PeriodicalIF":6.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modified alginates for precision drug delivery: Advances in controlled-release and targeting systems","authors":"Sara Masoumi Shahrbabak ,&nbsp;Seyede Melika Jalali ,&nbsp;Maryam Fadaei Fathabadi ,&nbsp;Vahid Tayebi-Khorrami ,&nbsp;Mostafa Amirinejad ,&nbsp;Soheil Forootan ,&nbsp;Mahsa Saberifar ,&nbsp;Mohammad Reza Fadaei ,&nbsp;Zohre Najafi ,&nbsp;Vahid Reza Askari","doi":"10.1016/j.ijpx.2025.100381","DOIUrl":"10.1016/j.ijpx.2025.100381","url":null,"abstract":"<div><div>Alginates have been modified to become a suitable platform for targeted drug release, triggering advances in targeted and controlled-release systems. Alginate chemistry and various structural modifications, including ionic crosslinking, cyclodextrin-linking, and chemical carboxyl and hydroxyl group modification, such as esterification, amidation, and sulfation, are covered in this review. These modifications are aimed at enhancing drug release mechanisms, like dissolution, diffusion, water penetration, and ion exchange-based systems. Application of modified alginates in controlled-release systems is extensive, from hydrogels, bioprinting approaches, nanofiber-based systems, in-situ gelling systems, to nanoparticle systems. Targeted drug delivery utilizes passive and active targeting strategies for numerous applications, including the treatment of cancer, inflammatory disease therapy, infectious disease, and wound healing. Emerging platforms such as hydrogels and nanoparticles provide evidence of the versatility of modified alginates. However, issues regarding scalability and biocompatibility remain as obstacles. In this review, the capabilities of alginate-based delivery systems and their role in making various release mechanisms for targeted delivery are discussed in relation to the future directions for precision medicine development.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100381"},"PeriodicalIF":6.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of 3D printed dexamethasone chewable tablets for prophylaxis of chemotherapy-induced nausea and vomiting in children","authors":"Adrin Dadkhah ,&nbsp;Tobias Gutowski ,&nbsp;Eva-Maria Wansing ,&nbsp;Alexander von Hugo ,&nbsp;Wilhelm Woessmann ,&nbsp;Beate Winkler ,&nbsp;Gefion Franke ,&nbsp;Michael Baehr ,&nbsp;Claudia Langebrake","doi":"10.1016/j.ijpx.2025.100380","DOIUrl":"10.1016/j.ijpx.2025.100380","url":null,"abstract":"<div><div>Dexamethasone (Dexa) is widely used for the prophylaxis of chemotherapy-induced nausea and vomiting. In pediatric patients, individual dosing often requires the manipulation of commercial tablets, leading to dose inaccuracies, higher treatment complexity and poor acceptance due to Dexa's intensely bitter taste.</div><div>This study aimed to develop 3D-printed chewable Dexa tablets with effective taste masking for pediatric oncology. Tablets were produced using semi-solid extrusion (SSE). The impact of excipients on printability and taste masking was evaluated, and the thermal stability of Dexa was assessed using DSC and TGA. Further assessments included disintegration, in vitro dissolution, content and mass uniformity, short-term stability and a sensory evaluation in healthy adult volunteers.</div><div>The tablets demonstrated excellent uniformity of mass (average RSD 0.75 %) and API content (99.35 % ± 2.92 %). Disintegration times ranged from 96 s (2 mg) to 733 s (12 mg). Complete drug release was achieved within 2 h. Thermal analysis showed no degradation of Dexa, and storage stability was confirmed for at least 5 weeks. A substantial reduction in bitterness was observed.</div><div>In conclusion, SSE enabled the reproducible production of child-appropriate, individually dosed Dexa chewable tablets with effective taste masking, supporting their clinical application in pediatric oncology.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100380"},"PeriodicalIF":6.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic nanocarriers for the therapy and management of intestinal inflammations","authors":"Rupam Bera ,&nbsp;Shivam Pathak ,&nbsp;Pradhi Srivastava ,&nbsp;Maitrayee Ghosh ,&nbsp;Anjana Sharma ,&nbsp;Noor Zaheer Ahmed ,&nbsp;Ritu Karwasra ,&nbsp;Usama Akram ,&nbsp;Pawan Kumar ,&nbsp;Bhupesh Sharma ,&nbsp;Nitin Sharma","doi":"10.1016/j.ijpx.2025.100377","DOIUrl":"10.1016/j.ijpx.2025.100377","url":null,"abstract":"<div><div>Intestinal inflammation particularly inflammatory bowel disease poses significant clinical challenges due to its chronic nature, limited treatment efficacy and adverse effects of conventional therapies like corticosteroids and biologics. Biomimetic nanocarriers have emerged as a transformative strategy to overcome these limitations by leveraging natural cell membranes for targeted drug delivery. This review critically examines the application of biomimetic nanocarriers as precision therapeutics for intestinal inflammation. We discuss key fabrication techniques including extrusion, sonication and microfluidics used to coat synthetic nanocarriers with membranes derived from several biological sources such as macrophages, neutrophils, platelets, stem cells and bacteria. These biomimetic coatings exploit inherent biological functions such as immune evasion, receptor-mediated binding to inflamed endothelium and responsiveness to inflammatory stimuli. Preclinical studies demonstrate that biomimetic nanocarriers effectively suppress pro-inflammatory pathways like NF-κB, NLRP3, sequester cytokines, promote mucosal healing and restore gut microbiota balance while minimizing systemic toxicity. Despite promising outcomes in animal models, clinical translation faces hurdles in membrane isolation standardization, long-term biosafety, and regulatory alignment. Future advancements require interdisciplinary efforts to optimize pharmacokinetics, enhance tissue-specific targeting, and integrate personalized designs. Biomimetic nanocarriers represent a paradigm shift toward disease-modifying therapies, offering potential for sustained remission in intestinal inflammation management.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100377"},"PeriodicalIF":6.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hesperidin-β-Cyclodextrin inclusion complexes: A novel approach for preventing and treating acute lung injury caused by seawater drowning","authors":"Jingjing Hou ,&nbsp;Mengdi Zhang ,&nbsp;Zheyi Han ,&nbsp;Wanmei Wang ,&nbsp;Haiying Qiu ,&nbsp;Jingwei Yuan ,&nbsp;Fang An ,&nbsp;Yan Wu","doi":"10.1016/j.ijpx.2025.100379","DOIUrl":"10.1016/j.ijpx.2025.100379","url":null,"abstract":"<div><div>Seawater drowning-induced acute lung injury (ALI) presents a significant challenge due to the lack of effective prevention and treatment strategies. Hesperidin (Hep) possesses diverse biological activities, including potent antioxidant and anti-inflammatory effects. However, its clinical utility is hindered by poor solubility and limited bioavailability. Therefore, there is an urgent need for the modification of hesperidin to enhance its water solubility and expand its therapeutic potential. In this study, an inhalable formulation of Hep-β-cyclodextrin inclusion complexes (Hep-β-CD) was developed as a promising approach for the management of seawater drowning-induced ALI. The cytotoxicity assessment in BEAS-2B cells revealed minimal adverse effects associated with Hep-β-CD. The administration of Hep-β-CD via the pulmonary route has been found to be highly effective in preventing seawater drowning-induced ALI in mice, achieved through modulation of key inflammatory mediators and a reduction in oxidative stress. The study demonstrated that Hep-β-CD administration significantly decreased the levels of pro-inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6), which are known to contribute to the pathogenesis of ALI. Additionally, the levels of malondialdehyde (MDA) were decreased and the levels of Superoxide Dismutase (SOD) were increased. In summary, the pulmonary delivery of Hep-β-CD was identified as a promising therapeutic strategy for preventing seawater drowning-induced ALI due to its ability to directly distribute the drug to the lungs, where it exerts a dual action of modulating the immune response to reduce inflammation and enhance the antioxidant defense mechanism.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100379"},"PeriodicalIF":6.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HSPiP and QbD oriented optimized nanocubosomes for ameliorated absorption of tolterodine tartrate: In vitro and in vivo evaluations","authors":"Afzal Hussain ,&nbsp;Tasneem Khan ,&nbsp;Mohd Usman Mohd Siddique ,&nbsp;Danishuddin ,&nbsp;Mohammad A. Altamimi ,&nbsp;Mohhammad Ramzan","doi":"10.1016/j.ijpx.2025.100378","DOIUrl":"10.1016/j.ijpx.2025.100378","url":null,"abstract":"<div><div>The study explored HSPiP and QbD-(quality by design) enabled optimized cubosomes for sustained drug release, improved permeation, and enhanced oral bioavailability. OCUB1 (the optimized product) was characterized for size, zeta potential (ZP), thermal analysis, and surface roughness. <em>In vitro</em> drug release and hemolysis studies were carried out using a dialysis membrane and rat erythrocytes (4 % suspension), respectively. An <em>ex vivo</em> non-everted intestinal permeation study (180 min) compared permeation potential between DS (suspension) and OCUB1. <em>In vivo</em> pharmacokinetic (PK) study investigated PK parameters in rats whereas hematological and biochemical assays ensured the safety of OCUB1. HSPiP predicted glyceryl monooleate (GMO), poloxamer−188, and polyvinyl alcohol (PVA) as optimal excipients based on minimum RED (relative energy difference) values while QbD identified OCUB1 as the most optimized formulation with desirable attributes such as low size (169 nm), high ZP (−29.2 mV), low polydispersity index (0.23), and maximum entrapment efficiency (85.3 %). Thermal analysis confirmed solubilization of TOTA in OCUB1, and atomic force microscopy (AFM) technique confirmed its cubical shape. OCUB1 showed extended drug release (98.1 % over 48 h) and sustained <em>ex vivo</em> permeation (<em>J</em>_<em>ss</em> = 6.69 μg/cm²/min, steady state flux) across rat intestine as compared to DS (<em>J</em>_<em>ss</em> = 9.172 μg/cm²/min). <em>In vivo</em> PK parameters exhibited significant improvement, with 3.2-fold increase in C_max as compared to the DS. <em>In vitro</em> hemolysis, along with biochemical and hematological assays, ensured the safety of OCUB1 for oral delivery. Conclusively, OCUB1 presents a promised alternative to conventional capsule, offering reduced side effects and enhanced patient compliance.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100378"},"PeriodicalIF":6.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}