International Journal of Pharmaceutics最新文献

{"title":"A four in one nanoplatform: Theranostic bismuth-containing nanoMOFs for chemo-photodynamic- radiation therapy and CT scan imaging.","authors":"Naeimeh Hassanzadeh Goji, Mona Alibolandi, Mohammad Ramezani, Amir Sh Saljooghi, Mahdieh Dayyani, Sirous Nekooei","doi":"10.1016/j.ijpharm.2024.124971","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124971","url":null,"abstract":"<p><p>Integration of different therapeutic performances into one platform is an innovative development for using multiple applications in real-time. In this paper, for the first time we exploited the concurrent capacity of radio and photosensitizing in a theranostic nanoMOFs based on bismuth, zirconium, and porphyrin. The porosity of nanoMOFs provided the capability of doxorubicin loading and chemotherapy besides enhanced photodynamic and radiation therapy (PDT & RT). Its PEGylation and aptamer (MUC1) immobilization endowed the platform with high biocompatibility and targeted tumor killing, respectively. In vitro assay exhibited that this aptamer immobilized DOX-loaded PEGylated MOF (Apt@DOX) produced more toxicity against 4 T1 cells compared to non-targeted nanoparticles (NP@DOX), especially when the treatment combined with PDT or/and RT. In vivo experiment also provided great results for tumor growth, survival rate, and body weight for 4 T1 bearing mice injected by Apt@DOX in combination with irradiation by 660 nm laser and/or exposure to 3 Gy dosage of X-ray radiation. The CT imaging of injected mice with targeted and non-targeted bismuth-based MOF introduced this nanoplatform as a promising CT contrast agent. Resultantly, we can present our as-synthesized nanoplatform as an efficient multifunctional theranostics with the ability of multimodal therapy and diagnostic performance.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124971"},"PeriodicalIF":5.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681689","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":"Cyclodextrin complexation as a fruitful strategy for improving the performance of nebivolol delivery from solid lipid nanoparticles.","authors":"P Mura, F Maestrelli, L M D Gonçalves, M Cirri, N Mennini, A J Almeida","doi":"10.1016/j.ijpharm.2024.124972","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124972","url":null,"abstract":"<p><p>Oral bioavailability of nebivolol (NEB), a highly-selective β1-adrenergic receptor antagonist specially used in hypertension treatment, is limited by its low aqueous solubility. In this work we investigated the possibility of developing a new effective oral formulation of NEB by exploiting a combined strategy based on NEB complexation with hydroxypropyl-βCyclodextrin (HPβCD) and complex incorporation into solid lipid nanoparticles (SLNs). Solubility studies enabled to choose Imwitor 491 and 988 as solid lipids for SLN preparation. The effect of their separated or combined use, at different amounts, and of different surfactants on nanoparticles dimensions, homogeneity and surface charge was examined. The best formulations were selected for drug loading, as such or as complex with HPβCD, and evaluated for physicochemical properties, morphology, entrapment efficiency and drug release. A comparison of the two kinds of formulations revealed that the presence of HPβCD improved SLNs quality in terms of reduced dimensions, higher homogeneity and greater physicochemical stability, avoiding the sharp Zeta Potential reduction observed when loading the plain drug; moreover, it allowed a marked increase in entrapment efficiency and better control of drug release. Furthermore, the use of HPβCD gave the opportunity of doubling drug loading without noticeable variations in SLNs physicochemical properties and maintaining excellent entrapment efficiency.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124972"},"PeriodicalIF":5.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681695","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":"Machine learning strengthened formulation design of pharmaceutical suspensions.","authors":"Nadina Zulbeari, Fanjin Wang, Sibel Selyatinova Mustafova, Maryam Parhizkar, René Holm","doi":"10.1016/j.ijpharm.2024.124967","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124967","url":null,"abstract":"<p><p>Many different formulation strategies have been investigated to oppose suboptimal treatment of long-term or chronic conditions, one of which are the nano- and microsuspensions prepared as long-acting injectables to prolong the release of an active pharmaceutical compound for a defined period of time by regulating the size of particles by milling. Typically, surfactant and/or polymers are added in the dispersion medium of the suspension during processing for stabilization purposes. However, current formulation investigations with milling are heavily based on prior expertise and trial-and-error approaches. Various interacting parameters such as the milling bead size, stabilizer type and concentration have confounded the investigation of milling process. The present study systematically exploited statistical and machine learning (ML) strategies to understand the relationship between suspension characteristics and formulation parameters under full-factorial milling experiments. Stabilizer concentration was identified as a significant factor (p < 0.001) for median suspension diameter (D₅₀). A formulation stability classification ML model with high prediction accuracy (0.91) and F1-score (0.91) under 10-fold cross-validation was constructed based on 72 formulation datapoints. Model interpretation through Shapley additive explanations (SHAP) revealed the prominent impact of stabilizer concentration and milling bead size on formulation stability. The present work demonstrated the potential to achieve a deeper understanding of the design and optimization of nano- and microsuspensions through explainable ML modelling on formulation screening data.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124967"},"PeriodicalIF":5.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681741","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":"Solution-mediated phase transformation of cocrystals at the solid-liquid interface: Relationships between the supersaturation generation rate and transformation pathway.","authors":"Runhui Fan, An Chen, Yang Yu, Ting Cai, Minshan Guo","doi":"10.1016/j.ijpharm.2024.124969","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124969","url":null,"abstract":"<p><p>Cocrystals easily undergo solution-mediated phase transformation at the surface of dissolving cocrystals during dissolution, which significantly deteriorates the solubility advantage of cocrystals. Here, a new scenario for the phase transformation of liquiritigenin (LQ) cocrystals in which the boundary of phase transformation diffuses along the surface to the bulk of the cocrystal was identified. Additionally, depending on the rate of supersaturation generation, phase transformation processes to the anhydrate and hydrate of LQ compete during cocrystal dissolution. The liquiritigenin - nicotinamide (LQ - NIC) cocrystal yielded a higher supersaturation rate, causing the nucleation kinetics to dominate the recrystallization process and the formation of a metastable form of LQ. However, in the liquiritigenin - isoniazid (LQ - INZ) cocrystal, the low supersaturation rate leading to recrystallization was controlled by thermodynamics and the subsequent formation of monohydrates of LQ (less soluble). As a result, in plain buffer, a multistep pathway for phase transformation of the LQ - NIC cocrystal was observed, in which the cocrystal was first converted into the anhydrate LQ (metastable form) and subsequently transformed into LQ·H₂O. A one-step phase transformation was observed for the LQ - INZ cocrystal, where the cocrystal was directly converted to LQ·H₂O. In a buffer containing the Eudragit E100 additive, for the LQ - NIC cocrystal, the dissolution performance improved, which can presumably be attributed to the solubilization effect of E100 on the anhydrate and the inhibitory effect on the transformation of the anhydrate to the monohydrate. However, for the LQ - INZ cocrystal, a negligible improvement in drug concentration was observed in the presence of E100 because of the slight effects of E100 on the solubility of LQ·H₂O. These findings provide valuable insights into the phase transformation pathways of cocrystals at the liquid-solid interface and the effects of additives on the dissolution behavior of cocrystals.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124969"},"PeriodicalIF":5.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681761","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":"Liposomes-mediated enhanced antitumor effect of docetaxel with BRD4-PROTAC as synergist for breast cancer chemotherapy/immunotherapy.","authors":"Xixi Chen, Fang Li, Binghui Cui, Qingyi Yan, Caisheng Qiu, Zengyan Zhu, Lijuan Wen, Weiliang Chen","doi":"10.1016/j.ijpharm.2024.124973","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124973","url":null,"abstract":"<p><p>It has been reported that proteolysis-targeting chimeras (PROTACs) can effectively degrade intracellular oncogenic proteins, providing an ideal strategy for cancer treatment. ARV825, a bromodomain-containing protein 4 (BRD4)-PROTAC, has demonstrated the capacity to enhance the antitumor effect of the classic chemotherapeutic agent docetaxel (DTX). However, there are three major challenges to the broader in vivo application of ARV825: poor solubility, poor permeability, and off-target effects. Additionally, the efficient co-delivery of ARV825 and DTX to tumor tissues for a synergistic therapeutic effect remains unresolved. In this study, liposomes were utilized as co-delivery vehicles for ARV825 and DTX to effectively address these issues. The well-established liposomes significantly improved the solubility of both ARV825 and DTX while maintaining a sustained release profile in blood-mimetic conditions. The co-loaded liposomes accumulated in tumor tissues via the enhanced permeability and retention (EPR) effect. After internalization, ARV825 effectively degraded intracellular BRD4 proteins and downregulated the expression of both Bcl-2 and PD-L1 proteins, thereby increasing tumor cell apoptosis and enhancing the tumor immune response. This, in turn, augmented the antitumor effect of DTX in vivo without undesired side effects. In conclusion, BRD4-PROTAC may serve as a promising synergistic agent alongside the conventional chemotherapeutic agent DTX, with liposomes functioning as effective co-delivery vehicles.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124973"},"PeriodicalIF":5.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681651","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":"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":"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 J 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":"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, ethyl cellulose, hydroxypropyl cellulose, and polyvinylpyrrolidone, 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":"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":"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":"2024-11-16","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}