International Journal of Pharmaceutics最新文献

{"title":"Multifunctional nanomaterial-mediated tumor therapeutics: enhancing efficacy and specificity","authors":"Sujin Kim ,&nbsp;Hwan D. Kim","doi":"10.1016/j.ijpharm.2025.125982","DOIUrl":"10.1016/j.ijpharm.2025.125982","url":null,"abstract":"<div><div>Cancer is the leading cause of death worldwide, and its burden is rapidly increasing with the aging population. Conventional treatment methods often cause side effects such as metastasis, multidrug resistance, and damage to surrounding healthy tissues. In recent years, with the rapid development of nanotechnology, nanomaterials have been explored for tumor treatment. Due to the large specific surface area, nanomaterials have a high drug-loading capacity and an advantageous size that allows them to pass through the cell barrier. In addition, they can prolong drug residence time and prevent rapid drug decomposition. Nanomaterials can exist in various forms depending on their shape, with their use varying based on the application. Currently, the use of nanomaterials in tumor treatment often requires modification to enhance their versatility. This review summarizes the development and application of modified nanomaterial-based multifunctional tumor therapeutic agents for tumor treatment.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"682 ","pages":"Article 125982"},"PeriodicalIF":5.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682550","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":"Effects of electrostatic charge on particle adhesion, powder cohesiveness and its alternative influences on powder flow properties","authors":"Tong Deng,&nbsp;Vivek Garg,&nbsp;Michael S.A. Bradley","doi":"10.1016/j.ijpharm.2025.125986","DOIUrl":"10.1016/j.ijpharm.2025.125986","url":null,"abstract":"<div><div>Characterising powder flowability for handling process is important but can be particularly challenging if only a small quantity of samples is available. A novel method developed at the Wolfson Centre uses only a few milligrams of samples to predict powder flow properties by Bond number — a representation of powder cohesiveness at the median size of particles by measuring particle adhesion. A good agreement between this method and the results using conventional shear cell testers has been found across various powders and formulations. However, recent investigations on acetaminophens revealed a discrepancy: predictions based on the Bond number did not align with the shear cell test results, suggesting the presence of additional contributing forces during the Bond number measurement.</div><div>As the Bond number is determined by assessing particle adhesion, it was hypothesised that electrostatic forces could influence the adhesion results and therefore the Bond number. This study focused on the electrostatic charge measurements of two grades of acetaminophen (dense and micronised) with differing particle sizes. For a comparison, common excipients such as lactose, magnesium stearate, and calcium carbonate were also evaluated, all of which previously exhibited good predictive correlations. Results show that acetaminophen samples exhibited charge levels up to 20 times higher than the excipient materials. It is inferred that electrostatic forces can strongly influence particle adhesion, if charge is significant, though their effect appears negligible in shear cell testing. The study concludes that electrostatic forces can significantly contribute to particle adhesion and impact powder flow behaviour particularly at low consolidation stresses.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"682 ","pages":"Article 125986"},"PeriodicalIF":5.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682549","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":"Integrating microfluidics and streamlined remote drug loading: one step closer to continuous manufacturing of liposomal injectables containing small drugs","authors":"Mariana Biscaia-Caleiras ,&nbsp;Diana Lopes ,&nbsp;Carolina Henriques ,&nbsp;Ana Sofia Lourenço ,&nbsp;António Nunes ,&nbsp;Manuel Bañobre ,&nbsp;João Nuno Moreira ,&nbsp;Sérgio Simões","doi":"10.1016/j.ijpharm.2025.125973","DOIUrl":"10.1016/j.ijpharm.2025.125973","url":null,"abstract":"<div><div>The industrial manufacturing of liposomal injectables faces significant technical challenges. Traditional batch manufacturing methods, like ethanol injection and extrusion, are time-consuming, prompting a shift towards continuous manufacturing. To improve process efficiency, this study tested microfluidics, a technique widely used in lipid nanoparticle (LNP) production for nucleic acid delivery, to optimize doxorubicin liposome manufacturing, focusing on vesicle formation and remote drug loading. The formulation consisted of neutral phospholipids with minimal DSPE-PEG content and no negatively charged lipids, components typically considered critical for liposome self-assembly and colloidal stability, demonstrating that microfluidics can effectively produce stable liposomes under these challenging conditions. Detailed characterization by cryo-TEM confirmed the formation of unilamellar vesicles with internal drug nanocrystals by microfluidics. In addition, it yielded fewer multilamellar liposomes than the conventional process (18 % vs. 35 %), indicating better control of vesicle structure and lamellarity. Importantly, employing microfluidics instead of ethanol injection and extrusion reduced liposome formation time by 70 % while ensuring consistent particle size distribution, relative to ethanol injection and extrusion. Additionally, lowering the temperature during drug loading (45 °C vs. 65 °C) shortened this step by 20 %, due to faster heating and cooling. Consequently, the optimized process was at least 25 % faster and reduced cost by 15 %. Although conducted at a 100 mL scale, these improvements are expected to be amplified on an industrial scale. Hence, these findings highlight the relevance of decreasing process temperatures and underscore the potential of microfluidics to enhance the efficiency and scalability of continuous manufacturing of liposomes for small molecular weight drug delivery, a field in which this technology has been underexplored.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"682 ","pages":"Article 125973"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674715","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":"Calcium phosphate nanoparticles efficiently deliver miR-205-5p to modulate oncogenic targets in prostate cancer cells","authors":"Anne Natalie Prigol ,&nbsp;Adny Henrique Silva ,&nbsp;Michele Patrícia Rode ,&nbsp;Hellen Karine Stulzer ,&nbsp;Lissette Alicia Cruz ,&nbsp;Daniel D. Carson ,&nbsp;Mary C. Farach-Carson ,&nbsp;Frederico Pittella ,&nbsp;Tânia Beatriz Creczynski-Pasa","doi":"10.1016/j.ijpharm.2025.125984","DOIUrl":"10.1016/j.ijpharm.2025.125984","url":null,"abstract":"<div><div>Prostate cancer (PCa) at the bone metastatic stage remains a global health challenge with low survival rates. This study aimed to identify therapeutic microRNAs (miRNAs) for delivery by calcium phosphate nanoparticles (CaP-NPs) to modify transcript profiles in PCa. Microarray analysis identified miR-205-5p as differentially downregulated in PCa bone metastatic cells (PC-3). CaP-NPs containing mimetic molecules of miR-205-5p were successfully prepared. Particles were spherical, sterile, and homogeneous and measured approximately 50 nm. CaP-NPs efficiently delivered miR-205-5p to cells, restoring its expression and inducing cell death. Transcript levels of the target genes <em>AR</em>, <em>BAMBI</em>, <em>SMAD1/5/9</em>, <em>VEGFA</em>, and <em>ZEB1</em> decreased following miR-205-5p delivery. Live-cell imaging demonstrated the uptake of CaP-NPs in both two-dimensional (PC3-cells monolayer culture) and three-dimensional (C4-2B-derived microtumor) cancer models. The three-dimensional model was produced in a microwell system inoculated with C4-2B cells, which readily form microtumors resembling disseminated PCa cells. Collectively, these results confirm miR-205-5p as a tumor suppressor in bone metastatic PCa cells and suggest that CaP-NPs could be a promising delivery system for further preclinical exploration in gene therapy targeting bone metastatic PCa.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"682 ","pages":"Article 125984"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674714","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 “Development of a stable inhalable dry powder formulation with osteoglycin fragment for alveolar epithelial repair” [Int. J. Pharm. 682 (2025) 125913]","authors":"Luke van der Koog ,&nbsp;Evalyne M Jansen ,&nbsp;Robin A.B. Elferink ,&nbsp;Sophie I.T. Bos ,&nbsp;Anika Nagelkerke ,&nbsp;Reinoud Gosens ,&nbsp;Henderik W. Frijlink ,&nbsp;Wouter L.J. Hinrichs","doi":"10.1016/j.ijpharm.2025.125968","DOIUrl":"10.1016/j.ijpharm.2025.125968","url":null,"abstract":"","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"682 ","pages":"Article 125968"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663297","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":"Advanced biomaterials in immune modulation: The future of regenerative therapies","authors":"Nazila Biglari ,&nbsp;Mahmood Razzaghi ,&nbsp;Yalda Afkham ,&nbsp;Ghazal Azimi ,&nbsp;Jeffrey D. Gross ,&nbsp;Ali Samadi","doi":"10.1016/j.ijpharm.2025.125972","DOIUrl":"10.1016/j.ijpharm.2025.125972","url":null,"abstract":"<div><div>Healing of tissue is a complex process controlled by immune responses in the forms of inflammatory, proliferative, and remodeling stages. Dysregulated immunity can interfere with healing and lead to fibrosis or chronic inflammation. Biomaterials engineered for immune modulation offer novel approaches to regulate immune responses and enhance tissue repair. This review explores biomaterials including natural polymers, synthetic hydrogels, and composites that modulate immune activity <em>via</em> bioactive molecule release, immune cell interaction, and surface functionalization. Advances in nanotechnology enable precise immune modulation through nanoparticle-based drug delivery and nanostructured surfaces. Uses range from bone repair, wound healing, and organ restoration where immunomodulatory biomaterials maximize integration and minimize rejection risks. Despite demonstrated benefits, challenges remain in ensuring biocompatibility, scalability, and regulatory approval. Future directions include smart biomaterials, artificial intelligence (AI)-driven design, and personalized approaches tailored to patient-specific immune profiles. Interdisciplinary collaboration among immunologists, materials scientists, and clinicians is essential for translating these innovations into clinical practice. Immunomodulatory biomaterials hold great potential to revolutionize tissue healing and address critical global healthcare challenges.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"682 ","pages":"Article 125972"},"PeriodicalIF":5.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667626","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":"Physiologically based pharmacokinetic modelling of in vitro skin permeation of sunscreen actives under various experimental conditions","authors":"Yuri Dancik ,&nbsp;Yanling Zhang ,&nbsp;Krishna C. Telaprolu ,&nbsp;Sebastian Polak","doi":"10.1016/j.ijpharm.2025.125977","DOIUrl":"10.1016/j.ijpharm.2025.125977","url":null,"abstract":"<div><div><em>In vitro</em> permeation testing (IVPT) is widely used in pharmaceutical and cosmetic formulation design and in safety assessment of topical products. The U.S. FDA recommends IVPT to screen sunscreen formulations prior to conducting a maximum usage trial (MUsT). For potential permeants such as highly lipophilic UV filters, designing IVPT protocols is a time- and resource-intensive trial-and-error process. Frequently used in clinical pharmacokinetics, physiologically based pharmacokinetic (PBPK) models can also emulate IVPT experiments. We present a PBPK modelling framework simulating the <em>in vitro</em> skin absorption of avobenzone, octocrylene, and oxybenzone investigated using different formulations, applied doses, and skin types. Combining bottom-up parameter predictions with optimizations relevant to changing experimental conditions, the models predict observed receptor cumulative and skin retention amounts within 2-fold and recover the variability obtained in experiments featuring suitable donor/replicate numbers and mass balances. The framework presented herein paves the way for greater integration of PBPK modelling into the design and interpretation of IVPT experiments and, ultimately, towards the design of MUsTs.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"682 ","pages":"Article 125977"},"PeriodicalIF":5.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667628","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":"Influence of filament loading technique on surrogate active pharmaceutical ingredient particle emissions during material extrusion 3D printing of tablets","authors":"Aleksandr B. Stefaniak ,&nbsp;Lauren N. Bowers ,&nbsp;Elizabeth D. Brusak ,&nbsp;Robert P. Streicher ,&nbsp;Alvaro Goyanes ,&nbsp;Sherri A. Friend ,&nbsp;Duane R. Hammond ,&nbsp;Ryan F. LeBouf ,&nbsp;Chaolong Qi ,&nbsp;M.Abbas Virji","doi":"10.1016/j.ijpharm.2025.125980","DOIUrl":"10.1016/j.ijpharm.2025.125980","url":null,"abstract":"<div><div>3D printing holds great promise to revolutionize pharmaceutical manufacturing, so for widespread clinical application, it is imperative to evaluate its safety and maximize its benefits. Herein, for the first time, particle emissions of the printing process of a model drug (fluorescein) were monitored in a test chamber to evaluate release. A filament extrusion-type 3D printer was used to make tablets from filaments loaded with fluorescein prepared by hot melt extrusion (HME) or diffusion (passive loading) techniques. Surface contamination of the printer was qualitatively documented. Average concentrations of fluorescein released into air during printing were below the analytical limit of detection for HME and 0.92 ± 0.20 ng/m³ for diffusion. Particle yield from the aerodynamic particle sizer data (#/g extruded) during printing with HME filament (5.01 x 10⁴) was significantly lower (p &lt; 0.05) compared with diffusion filament (1.07 x 10⁶). Mathematical modeling was used to predict where particles might deposit in the respiratory system if inhaled by a worker. Predictions showed larger fractions of particles deposited in the head and pulmonary (alveolar) regions from diffusion-loaded filament compared with HME, albeit non-significant. Fluorescein was transferred onto personal protective equipment (gloves) and printer surfaces, which indicated potential for dermal exposure and cross-contamination. Assuming our results are representative of active pharmaceutical ingredients, they support the importance of controls such as containment to minimize inhalation exposure and housekeeping to minimize dermal exposure and cross-contamination of tablets.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"682 ","pages":"Article 125980"},"PeriodicalIF":5.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667627","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 and evaluation of a prostate-targeting wild chrysanthemum rectal heating gel for prostatitis treatment","authors":"Hua Sheng ,&nbsp;Xue Han ,&nbsp;Xin Wang ,&nbsp;Xiushan Liu ,&nbsp;Haozhou Huang ,&nbsp;Yanmei Sheng ,&nbsp;Dingkun Zhang ,&nbsp;Xingliang Xie","doi":"10.1016/j.ijpharm.2025.125975","DOIUrl":"10.1016/j.ijpharm.2025.125975","url":null,"abstract":"<div><div>This study aimed to develop a rectal heating gel for targeted treatment of prostatitis, on the basis of the synergistic effects of wild chrysanthemum (<em>Chrysanthemu indicum</em>) extract (rich in buddleoside and chlorogenic acid) and a phase-change microemulsion (PCME). A microemulsion system was developed with n-docosane serving as the thermal energy storage medium. The PCME was systematically characterized for particle size, stability, phase transition temperature, as well as heat-retention capacity. Results demonstrated good stability, with a phase transition temperature of 42.94–43.57 °C and latent heat of 98.43–100.41 J/g, capable of sustaining heat release for 30 min under simulated physiological conditions. Upon external heating, the PCME efficiently stored thermal energy; subsequently, following rectal administration, the incorporated system delivered prolonged and gentle thermotherapy at physiological temperature. Sodium carboxymethyl cellulose (CMC-Na) was selected as the mucoadhesive gel matrix to co-load the extract and PCME. Additionally, the optimized formulation contained 8.0 % extract, 75.5 % PCME, 1.2 % CMC-Na, and 15.3 % water. <em>In vitro</em> release studies indicated 69.21 % buddleoside and 93.73 % chlorogenic acid release over 12  h, with mucosal permeation rates of 69.92 % and 93.70 %, respectively. Animal studies revealed no notable irritation to the rectum or prostate, while significantly enhancing drug accumulation and peak concentration within prostatic tissue. Compared to conventional formulations, the heating gel more effectively decreased the prostate index and inhibited inflammatory cytokine expression, underscoring its synergistic efficacy in localized thermotherapy combined with targeted phytomedicine delivery. This innovative gel formulation is structurally stable, easy to administer, and dual-functional, representing a promising therapeutic candidate for the management of chronic prostatitis.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"682 ","pages":"Article 125975"},"PeriodicalIF":5.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655825","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":"From barriers to breakthroughs: Mesoporous silica nanoparticles in targeting the tumor microenvironment","authors":"Adel Mahmoudi Gharehbaba ,&nbsp;Fatemeh Soltanmohammadi ,&nbsp;Morteza Eskandani ,&nbsp;Khosro Adibkia","doi":"10.1016/j.ijpharm.2025.125979","DOIUrl":"10.1016/j.ijpharm.2025.125979","url":null,"abstract":"<div><div>The tumor microenvironment (TME) comprises various components that critically influence cancer progression, metastasis, and resistance to therapy, making it a key focus for developing innovative cancer treatments. Mesoporous silica nanoparticles (MSNs) have gained attention as a promising drug delivery platform due to their unique properties, such as high surface area, adjustable pore size, and ease of functionalization. This review delves into the intricate relationship between the TME and cancer progression, emphasizing the physiological and biochemical barriers that impede effective drug delivery. We explore the latest developments in MSN-based approaches aimed at modulating the TME. These strategies focus on mitigating hypoxia, counteracting acidic pH levels, disrupting the tumor vasculature, and targeting key stromal elements such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). Additionally, we investigate the potential of MSNs to suppress the Warburg effect and enhance immunotherapy outcomes. By addressing these critical challenges, MSNs offer a highly adaptable platform for enhancing the specificity and effectiveness of cancer therapeutics. This review underscores the groundbreaking potential of MSNs in reconfiguring the TME and driving progress in personalized cancer treatment strategies.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"682 ","pages":"Article 125979"},"PeriodicalIF":5.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663296","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}