International Journal of Pharmaceutics最新文献

{"title":"Tricomponent immunoactivating nanomedicine to downregulate PD-L1 and polarize macrophage for photodynamic immunotherapy of colorectal cancer.","authors":"Renjiang Kong, Jiaqi Huang, Yeyang Wu, Ni Yan, Xin Chen, Hong Cheng","doi":"10.1016/j.ijpharm.2024.124968","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124968","url":null,"abstract":"<p><p>The unsatisfactory immunotherapeutic responses are primarily attributed to the insufficient immune recognition and the presence of an immunosuppressive tumor microenvironment (ITM). This study focuses on the development of a tricomponent immunoactivating nanomedicine called TIN that combines a photosensitizer, an inhibitor of epidermal growth factor receptor (EGFR) and a CSF-1R inhibitor to enable photodynamic immunotherapy by downregulating PD-L1 expression and repolarizing tumor-associated macrophages (TAMs). TIN is designed to facilitate the drug delivery and target specific pathways involved in tumor progression. By inhibiting the activity of EGFR and CSF-1R, TIN reduces PD-L1 expression on tumor cells and induces the TAMs polarization to M1 phenotype, restoring the immune recognition of T cells and the phagocytosis of macrophage to reshape the immunosuppressive microenvironment. Additionally, the photodynamic therapy (PDT) of TIN can greatly destroy the primary tumor and trigger immunogenic cell death (ICD). Importantly, the immune checkpoint blockade effect of TIN can enhance the immune response of PDT-induced ICD for metastatic tumor treatment. This study presents a self-assembling strategy for the development of an all-in-one nanomedicine, effectively integrating multiple therapeutic modalities to provide a comprehensive and systemic approach for tumor suppression.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124968"},"PeriodicalIF":5.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675784","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":"Exploring the impact of material selection on the efficacy of hot-melt extrusion.","authors":"Devesh U Kapoor, Devendra K Vaishnav, Rahul Garg, Pushpendra Kumar Saini, Bhupendra G Prajapati, Guillermo R Castro, Supakij Suttiruengwong, Sontaya Limmatvapirat, Pornsak Sriamornsak","doi":"10.1016/j.ijpharm.2024.124966","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124966","url":null,"abstract":"<p><p>Hot-melt extrusion (HME) has emerged as a versatile and efficient technique in pharmaceutical formulation development, particularly for enhancing the solubility and bioavailability of poorly water-soluble drugs. This review delves into the fundamental principles of HME, exploring its application in drug delivery systems. A comprehensive analysis of polymers utilized in HME, such as hydroxypropyl methylcellulose (HPMC), ethyl cellulose, hydroxypropyl cellulose (HPC), and polyvinylpyrrolidone (PVP), is presented, highlighting their roles in achieving controlled drug release and improved stability. The incorporation of plasticizers, such as triacetin, poly(propylene glycol), glycerol, and sorbitol, is critical in reducing the glass transition temperature (T_g) of polymer blends, thereby enhancing the processability of HME formulations. A comparison of T_g values for various polymer-plasticizer combinations is discussed using different predictive models. For researchers and industry professionals looking to optimize drug formulation strategies, this article offers valuable insights into the mechanisms through which HME enhances drug solubility and bioavailability two critical factors in oral drug delivery. Furthermore, by reviewing recent patents and marketed formulations, the article serves as a comprehensive resource for understanding both the technical advancements and commercial applications of HME. Readers will gain a deep understanding of the role of polymers and additives in HME, alongside future perspectives on how emerging materials and techniques could further revolutionize pharmaceutical development. This review is essential for those aiming to stay at the forefront of pharmaceutical extrusion technologies and their potential to improve therapeutic outcomes. The review concludes that meticulous material selection is vital for advancing pharmaceutical manufacturing processes and ensuring optimal outcomes in HME applications, thereby enhancing the overall efficacy of drug delivery systems.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124966"},"PeriodicalIF":5.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675782","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":"Corrigendum to \"Evaluation of binders in twin-screw wet granulation - Optimization of tabletability\" [Int. J. Pharm. 659 (2024) 124290].","authors":"Claudia Köster, Peter Kleinebudde","doi":"10.1016/j.ijpharm.2024.124939","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124939","url":null,"abstract":"","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124939"},"PeriodicalIF":5.3,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647474","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":"Posaconazole nanocrystals dry powder inhalers for the local treatment of invasive pulmonary aspergillosis.","authors":"Xuchun Li, Qing Wang, Jiewen Huang, Xiao Yue, Xuejuan Zhang, Xinxin Fan, Zhian Fang, Guanlin Wang, Zhenwen Qiu, Dandong Luo, Qiupin Guo, Alan Xiaodong Zhuang, Shaofeng Zhan, Qingguo Li, Ziyu Zhao","doi":"10.1016/j.ijpharm.2024.124938","DOIUrl":"10.1016/j.ijpharm.2024.124938","url":null,"abstract":"<p><p>Invasive pulmonary aspergillosis poses a significant threat to immunocompromised patients, characterized by high mortality rates. Posaconazole (PSZ), a second-generation triazole antifungal, exhibits broad-spectrum activity but suffers from limited pulmonary concentrations and notable systemic side effects when administered orally or intravenously. This study focuses on optimizing PSZ nanocrystals-agglomerated particles for dry powder inhalers (DPIs) to enhance solubility, dissolution rates, and pulmonary deposition, ultimately improving therapeutic efficacy while minimizing systemic adverse effects. We employed wet medium milling and spray-drying techniques to formulate PSZ nanocrystals-agglomerated DPIs. Various stabilizers including HPMC, HPC, Soluplus, and PVPK30, were systematically evaluated to optimize physicochemical properties. Aerosolization performance was assessed using the Next Generation Impactor, while antifungal efficacy was evaluated through in vitro and in vivo studies The optimized PSZ DPIs demonstrated significant enhancements in solubility and dissolution rates, with a fine particle fraction (FPF) of 78.58 ± 3.21 %, ensuring optimal lung delivery. In vitro experiments revealed potent effects with minimal cytotoxicity to lung cells. In vivo studies indicated that the optimized formulation achieved a C_max/AUC_0→∞ ratio in lung tissues that was 27.32 and 6.76-fold higher than that of the oral suspension, highlighting increased local drug concentrations. This approach presents a scalable, cost-effective strategy for the pulmonary delivery of PSZ, ensuring high drug loading and promising clinical outcomes in treating pulmonary fungal infections.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124938"},"PeriodicalIF":5.3,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667352","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":"Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing.","authors":"Gloria Mora-Castaño, Lucía Rodríguez-Pombo, Paola Carou-Senra, Patricija Januskaite, Carlos Rial, Carlos Bendicho-Lavilla, Maria L Couce, Mónica Millán-Jiménez, Isidoro Caraballo, Abdul W Basit, Carmen Alvarez-Lorenzo, Alvaro Goyanes","doi":"10.1016/j.ijpharm.2024.124964","DOIUrl":"10.1016/j.ijpharm.2024.124964","url":null,"abstract":"<p><p>Biotinidase deficiency is a rare inherited disorder characterized by biotin metabolism issues, leading to neurological and cutaneous symptoms that can be alleviated through biotin administration. Three-dimensional (3D) printing (3DP) offers potential for personalized medicine production for rare diseases, due to its flexibility in designing dosage forms and controlling release profiles. For such point-of-care applications, rigorous quality control (QC) measures are essential to ensure precise dosing, optimal performance, and product safety, especially for low personalized doses in preclinical and clinical studies. In this work, we addressed QC challenges by integrating a precision balance into a direct powder extrusion pharmaceutical 3D printer (M3DIMAKER™) for real-time, in-line mass uniformity testing, a critical quality control step. Small and large capsule-shaped biotin printlets (3D printed tablets) for immediate- and extended-release were printed. The integrated balance monitored and registered each printlet's weight, identifying any deviations from acceptable limits. While all large printlet batches met mass uniformity criteria, some small printlet batches exhibited weight deviations. In vitro release studies showed large immediate-release printlets releasing 82% of biotin within 45 min, compared to 100% for small immediate-release printlets. For extended-release formulations, 35% of the drug was released from small printlets, whereas 24% was released from large printlets at the same time point. The integration of process analytical technology tools in 3DP shows promise in enhancing QC and scalability of personalized dosing at the point-of-care, demonstrating successful integration of a balance into a direct powder extrusion 3D printer for in-line mass uniformity testing across different sizes of capsule-shaped printlets.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124964"},"PeriodicalIF":5.3,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667340","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":"Simultaneous prediction of the API concentration and mass gain of film coated tablets using Near-Infrared and Raman spectroscopy and data fusion.","authors":"Bence Szabó-Szőcs, Máté Ficzere, Orsolya Péterfi, Dorián László Galata","doi":"10.1016/j.ijpharm.2024.124957","DOIUrl":"10.1016/j.ijpharm.2024.124957","url":null,"abstract":"<p><p>This study investigates the simultaneous prediction of active pharmaceutical ingredient (API) concentration and mass gain in film-coated tablets using Partial Least Squares (PLS) regression combined with three data fusion (DF) techniques: Low-Level (LLDF), Mid-Level (MLDF), and High-Level (HLDF). Near-Infrared (NIR) and Raman spectroscopy were utilized in both reflection and transmission modes, providing four types of spectral data per tablet. Transmission models proved more effective for API prediction by capturing data from the entire tablet, while reflection models excelled in assessing mass gain by focusing on the surface layer. Among the DF strategies, MLDF with Principal Component Analysis (PCA) offered the most significant improvements in predictive accuracy by filtering out irrelevant information. Variable selection methods further enhanced model performance by reducing the number of latent variables required. Overall, the integration of multiple spectral datasets and DF techniques resulted in models that gave predictions for evaluation samples with lower errors, demonstrating their potential to optimize quality control in pharmaceutical manufacturing.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124957"},"PeriodicalIF":5.3,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667360","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":"Biodegradable lipid bilayer-assisted indocyanine green J- aggregates for photothermal therapy: Formulation, in vitro toxicity and in vivo clearance.","authors":"Wafa T Al-Jamal, Cristian Reboredo, Ubah Abdi, Pia Curci, Raghed Qadadeh, Hamoud Alotaibi, Luca Casettari, Taher Hatahet","doi":"10.1016/j.ijpharm.2024.124963","DOIUrl":"10.1016/j.ijpharm.2024.124963","url":null,"abstract":"<p><p>Indocyanine green (ICG) J-aggregates (IJA) are a unique form of aggregation that exhibits superior properties to monomeric ICG. Despite their higher photoacoustic (PA) signals for imaging and heating stability during photothermal therapy (PTT), they exhibit low stability under a biological milieu. Our group previously proposed a simple procedure for in-situ preparation of IJA into liposomes, accelerating their formation and optical properties. To comprehend their potential applications, we systematically investigated the effect of the lipid bilayer composition on ICG J-aggregation and stability. Moreover, their in vitro compatibility and photothermal toxicity in monolayers and cancer spheroids, besides their in vivo biodistribution and clearance were evaluated. Our findings revealed the importance of high cholesterol and PEG-lipid content and low charged lipids (∼ 5 mol %) in liposomes to promote a high IJA/ICG ratio and, thus, high heating stability. More importantly, IJA-liposomes revealed high biocompatibility in monolayer and cancer spheroids with efficient photothermal toxicity. Finally, IJA-liposomes were cleared from the body without toxicity. Interestingly, IJA-liposomes mainly showed lower affinity to the liver than monomeric ICG, resulting in higher renal clearance. Overall, our biodegradable IJA-liposomes could be an excellent alternative to gold-based agents suitable for PA imaging and cancer PTT.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124963"},"PeriodicalIF":5.3,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667223","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":"Neutrophil membrane-coated nanoparticles for targeted delivery of toll-like receptor 4 siRNA ameliorate LPS-induced acute lung injury.","authors":"Liang Cao, Min Du, Mengmeng Cai, Yan Feng, Juanjuan Miao, Jiafeng Sun, Jie Song, Boxiang Du","doi":"10.1016/j.ijpharm.2024.124960","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124960","url":null,"abstract":"<p><p>Pulmonary delivery of small interfering RNAs (siRNAs) is an effective treatment for acute lung injury (ALI), which can modulate the expression of pro-inflammatory cytokines and alleviate the symptoms of ALI. However, the rapid degradation of siRNA in vivo and its limited ability to target and validate cells are important challenges it faces in clinical practice. In this work, we developed neutrophil membrane-coated Poly (lactic-co-glycolic acid) nanoparticles loaded with TLR4 siRNA (si-TLR4) (Neutrophil-NP-TLR4), which can target both inflammatory and macrophage cells to alleviate the pulmonary inflammation in lipopolysaccharide (LPS)-induced ALI mice. These Neutrophil-NP-TLR4 effectively reduce the TNF-α and IL-1β expressions both in vitro and in vivo. Meanwhile, they also reduced the expression of TLR4, and its downstream genes including TNF receptor-associated factor 6 (TRAF6), X-linked inhibitor of apoptosis protein (XIAP), and Nuclear Factor kappa-B (NF-κB), but elevated the levels of Aquaporin 1 (AQP1) and Aquaporin 5 (AQP5). Moreover, the Neutrophil-NP-TLR4 precisely targets the inflammatory site to attenuate the lung injury without causing toxicity to normal tissue. This system provides a promising approach to effective delivery of siRNA to precisely treat the ALI.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124960"},"PeriodicalIF":5.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647606","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":"Dose sparing enabled by immunization with influenza vaccine using orally dissolving film","authors":"Keon-Woong Yoon ,&nbsp;Ki Back Chu ,&nbsp;Gi-Deok Eom ,&nbsp;Jie Mao ,&nbsp;Su In Heo ,&nbsp;Fu-Shi Quan","doi":"10.1016/j.ijpharm.2024.124945","DOIUrl":"10.1016/j.ijpharm.2024.124945","url":null,"abstract":"<div><div>Influenza vaccine delivered by orally dissolving film vaccine (ODFV) is a promising approach. In this study, we generated three ODFVs each comprising pulluan and trehalose with different doses of inactivated A/Puerto Rico/8/34, H1N1 virus (ODFV I, II, III) to evaluate their dose-sparing effect in mice. The ODFVs were placed on the tongues of mice to elicit immunization and after 3 immunizations at 4-week intervals, mice were challenged with a lethal dose of A/PR/8/34 to assess vaccine-induced protection. The 3 ODFVs containing 50, 250, or 750 μg of inactivated viruses elicited virus-specific antibody responses and virus neutralization in a dose-dependent manner. Dose-dependent antibody responses were also observed from the mucosal tissue samples, and also from antibody-secreting cells of the lungs and spleens. ODFV-induced cellular immunity, particularly germinal center B cells and T cells were also dose-dependent. Importantly, all 3 ODFVs evaluated in this study provided complete protection by strongly suppressing the pro-inflammatory cytokine production and lung virus titers. None of the immunized mice underwent noticeable weight loss nor succumbed to death, a phenomenon that was only observed in the infection challenge controls. These results indicated that the protection conferred by a low dose influenza vaccine formulated in ODF is comparable to that of a high-dose vaccine, thereby enabling vaccine dose sparing effect.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124945"},"PeriodicalIF":5.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643921","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":"Transfersomal serum loading amniotic mesenchymal stem cells metabolite products with hyaluronic acid addition for skin regeneration in UV aging-induced mice.","authors":"Andang Miatmoko, Syarifah Sutra Dewangga, Kevin Ksatria Handoko, Djoko Legowo, Kusuma Eko Purwantari, Joni Susanto, Arif Nurkanto, Purwati, Dini Retnowati, Margaret Ahmad, Widji Soeratri","doi":"10.1016/j.ijpharm.2024.124950","DOIUrl":"10.1016/j.ijpharm.2024.124950","url":null,"abstract":"<p><p>Amniotic Mesenchymal Stem Cells Metabolite Products (AMSC-MP) contain growth factors that benefit human health. This study aims to evaluate the use of transfersomal serum (Trans) with hyaluronic acid (HA) addition to deliver large molecules of AMSC-MP for skin regeneration. Trans is composed of L-α-phosphatidylcholine and surfactants, i.e., sodium cholate (SC) or stearylamine (SA), at the weight ratio of 85:15, prepared by the thin film method with or without HA addition. The results showed that HA addition increased the particle size of Trans-SA and Trans-SC, from 261.9 ± 1.9 and 105.3 ± 0.9 nm respectively, to 317.7 ± 9.1 and 144.3 ± 0.8 nm for Trans-SA-HA and Trans-SC-HA. In contrast, no significant changes in the zeta potential occurred. The relative deformability indexes of Trans-SA, Trans-SA-HA, Trans-SC, and Trans-SC-HA compared to liposome were 0.43 ± 0.09, 0.46 ± 0.09, 1.58 ± 0.17, and 1.40 ± 0.17 respectively. The addition of HA successfully increases the in vivo skin hydration, collagen density, and number of fibroblast cells, reflecting the capacity for skin regeneration in UV-induced aged mice. Furthermore, no erythema or skin rash was observed at the 24-hour post-topical application sites. AMSC-MP transfersomal serum with HA addition successfully enhanced skin regeneration and proved safe during the in vivo study using UV aging-induced mice models, thereby enabling its potential use as skin-aging therapy.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124950"},"PeriodicalIF":5.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638955","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}