International Journal of Pharmaceutics最新文献

{"title":"Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 4: Experimental validation of the models of drug concentration in blood","authors":"Aron H. Blaesi ,&nbsp;Henning Richter ,&nbsp;Nannaji Saka","doi":"10.1016/j.ijpharm.2024.124363","DOIUrl":"10.1016/j.ijpharm.2024.124363","url":null,"abstract":"<div><div>In this final part, the models of drug concentration in blood developed in Part 3 are validated on dogs. Both gastroretentive fibrous and immediate-release particulate dosage forms containing 200 mg nilotinib were tested. After administering, the fibrous dosage form expanded linearly with time in the stomach, to about 1.5 times the initial radius by 4 hours. The expanded dosage form fractured after 10 hours, and then passed into the intestine. The drug concentration in blood exhibited a broad peak with a maximum of 0.51 μg/ml and a width at half-height of 10.2 hours. By contrast, after administering the immediate-release particulate dosage form the drug concentration in blood exhibited a sharp peak with a maximum of 0.68 μg/ml and a width at half-height of just 3.6 hours. The experimental data validate the theoretical models reasonably. Thus, upon repeated dosing, the gastroretentive fibrous dosage forms presented in this study enable a constant drug concentration in blood for enhancing the efficacy and mitigating side effects of cancer therapies.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 124363"},"PeriodicalIF":5.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436886","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":"Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 2: Experimental validation of the models of expansion, post-expansion mechanical strength, and drug release","authors":"Aron H. Blaesi ,&nbsp;Nannaji Saka","doi":"10.1016/j.ijpharm.2024.124361","DOIUrl":"10.1016/j.ijpharm.2024.124361","url":null,"abstract":"<div><div>In Part 1, we have introduced expandable gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. The expansion rate, post-expansion mechanical strength, and drug release rate were modeled for a dosage form containing 200 mg nilotinib. In the present part, the dosage form was prepared and tested <em>in vitro</em> to validate the models. Upon immersing in a dissolution fluid, the fibrous dosage form expanded at a constant rate to a normalized radial expansion of 0.5 by 4 hours, and then formed an expanded viscoelastic mass of high strength. The drug was released at a constant rate over a day. For comparison, a particle-filled gelatin capsule with the same amount of nilotinib disintegrated almost immediately, and released eighty percent of the drug content in just 10 minutes. The experimental data validate the theoretical models of Part 1 reasonably.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 124361"},"PeriodicalIF":5.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442665","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":"Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 1: Dosage form design, and models of expansion, post-expansion mechanical strength, and drug release","authors":"Aron H. Blaesi ,&nbsp;Nannaji Saka","doi":"10.1016/j.ijpharm.2024.124360","DOIUrl":"10.1016/j.ijpharm.2024.124360","url":null,"abstract":"<div><div>At present, the efficacy and safety of many cancer therapies employing a sparingly-soluble tyrosine kinase inhibitor (TKI) are compromised by excessive fluctuations in the drug concentration in blood. To mitigate this limitation, in this four-part study expandable, gastroretentive fibrous dosage forms that deliver drug into the gastric fluid (and into the blood) at a controlled rate for prolonged time are presented. The dosage form comprises a cross-ply structure of water-absorbing, high-molecular-weight hydroxypropyl methylcellulose (HPMC) based fibers coated with a strengthening, enteric excipient. The intervening spaces between the coated fibers are solid annuli of dispersed drug particles in a low-molecular-weight HPMC-based excipient matrix. The central regions of the annuli are open channels. In this part, models are developed for dosage form expansion, post-expansion mechanical strength, and drug release. The models suggest that upon immersing in a dissolution fluid, the fluid percolates the open channels, diffuses into the annuli and the coated fibers, and the dosage form expands. The expansion rate is inversely proportional, and the post-expansion mechanical strength proportional to the volume fraction of the coating. Drug particles are released from the annuli as the surrounding excipient dissolves. The drug release rate is proportional to the concentration of low-molecular-weight HPMC at the annulus/dissolution fluid interface. The dosage forms can be readily designed for expansion in a few hours, formation of a high-strength viscoelastic mass, and drug release at a constant rate over a day.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 124360"},"PeriodicalIF":5.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442664","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":"Withdrawal notice to “Impact of various electromagnetic fields on the transdermal permeability of naproxen and the effect of active compound exposure on magnetic field properties” [Int. J. Pharm. 674 (2025) 125475]","authors":"Rafał Rakoczy ,&nbsp;Karolina Zyburtowicz Ćwiartka ,&nbsp;Maciej Konopacki ,&nbsp;Anna Nowak ,&nbsp;Anna Muzykiewicz-Szymańska ,&nbsp;Łukasz Kucharski ,&nbsp;Marian Kordas ,&nbsp;Paula Ossowicz-Rupniewska","doi":"10.1016/j.ijpharm.2025.125564","DOIUrl":"10.1016/j.ijpharm.2025.125564","url":null,"abstract":"","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125564"},"PeriodicalIF":5.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795480","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":"Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 3: Theoretical models of drug concentration in blood","authors":"Aron H. Blaesi ,&nbsp;Nannaji Saka","doi":"10.1016/j.ijpharm.2024.124362","DOIUrl":"10.1016/j.ijpharm.2024.124362","url":null,"abstract":"<div><div>In this part, drug concentration in blood after ingesting gastroretentive fibrous and immediate-release particulate dosage forms is modeled. The tyrosine kinase inhibitor nilotinib, which is slightly soluble in low-pH gastric fluid but practically insoluble in pH-neutral intestinal fluid is used as drug. The models suggest that upon ingestion, the fibrous dosage form expands, is retained in the stomach for prolonged time, and releases drug into the gastric fluid at a constant rate. The released drug molecules flow into the duodenum with the gastric fluid, and are absorbed by the blood. The drug is eliminated from the blood by the liver at a rate proportional to its concentration. Thus, as the drug concentration in blood increases due to absorption, the elimination rate increases, too, and will eventually be the same as the absorption rate, so that the drug concentration in blood plateaus out. After the gastric residence time, drug absorption stops, and the drug concentration in blood drops to zero. By contrast, after administering the immediate-release particulate dosage form the drug particles are swept out of the stomach rapidly, and drug absorption stops much earlier. The drug concentration in blood rises and falls without attaining steady state. The gastroretentive fibrous dosage forms enable a constant drug concentration in blood for drugs that are insoluble in intestinal fluids.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 124362"},"PeriodicalIF":5.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431948","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":"LDLR-targeted orlistat therapeutic nanoparticles: Peptide selection, assembly, characterization, and cell-uptake in breast cancer cell lines","authors":"George Bebawy ,&nbsp;Pamela Collier ,&nbsp;Philip M. Williams ,&nbsp;Jonathan C. Burley ,&nbsp;David Needham","doi":"10.1016/j.ijpharm.2025.125574","DOIUrl":"10.1016/j.ijpharm.2025.125574","url":null,"abstract":"<div><h3>Motivation</h3><div>Many cancers overexpress low-density lipoprotein receptors (LDLR), facilitating cholesterol metabolism for tumour growth. Targeting LDLR offers a promising strategy for selective drug delivery. Orlistat, a fatty acid synthase (FAS) inhibitor, has shown anti-cancer potential, particularly in tumours with high FAS expression. This study introduces an LDLR-Orlistat Targeted Nanoparticles (LDLR-OTNs) to enhance cancer cell uptake via LDLR-mediated endocytosis. The objectives include synthesizing lipid-based orlistat nanoparticles, functionalizing them with an 11-mer LDLR-binding peptide, assessing uptake and cytotoxicity in three LDLR- and FAS-expressing breast cancer cell lines (BT-474, MDA MB 453, MCF-7), and comparing uptake kinetics with non-targeted nanoparticles.</div></div><div><h3>Methods</h3><div>Orlistat nanoparticles (ONs) were synthesised via rapid solvent exchange, producing uncoated ONs, POPC-coated ONs (POPC-ONs), and LDLR-targeted ONs (LDLR-OTNs). Targeting was achieved by conjugating an 11-mer binding peptide (RLTRKRGLKLA) to DSPE-PEG5000 maleimide via click chemistry, confirmed by Ellman’s test. Nanoparticles were characterised using DLS and TEM. Cellular uptake over 24 hours was assessed using fluorescence-labelled POPC-ONs and LDLR-OTNs, and uptake kinetics were analysed. Suramin-blocking studies were used to confirm LDLR-mediated uptake. A 48-hour cytotoxicity assay quantified IC₅₀ values in the aforementioned cell lines.</div></div><div><h3>Results</h3><div>TEM data showed that LDLR-OTNs (33 nm) were smaller than untargeted POPC-ONs (58 nm) and uncoated ONs (67 nm). Ellman’s test confirmed &gt; 99.2% peptide conjugation. Cellular uptake of LDLR-OTNs was rapid, with significant fluorescence by 1 hour and a kinetic plateau at 24–48 hours, with data fitting to a modified exponential model, while that of untargeted POPC-ONs had lower initial uptake, following a logistic model. Suramin blocking reduced LDLR-OTN uptake, confirming receptor-mediated entry. Cytotoxicity assays yielded IC₅₀ values of 23.8 µM (BT-474), 25.8 µM (MDA MB 453), and 8.2 µM (MCF-7), with maximal inhibition at 48 h.</div></div><div><h3>Conclusions</h3><div>LDLR-OTNs demonstrated receptor-mediated uptake and potent cytotoxicity in LDLR- and FAS- overexpressing breast cancer cells. These findings support LDLR-targeted nanoparticles as a promising approach for delivering FAS inhibitors to LDLR-rich tumours, meriting further investigation in targeted cancer therapy development.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125574"},"PeriodicalIF":5.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842984","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":"Bacterial exopolysaccharide and metal-doped bioactive glass nanoparticles-based electrospun membranes for chronic wound healing","authors":"Sihame Akhtach ,&nbsp;Zakaria Tabia ,&nbsp;Rajae Belkhou ,&nbsp;Khalil El Mabrouk","doi":"10.1016/j.ijpharm.2025.125594","DOIUrl":"10.1016/j.ijpharm.2025.125594","url":null,"abstract":"<div><div>Healing of chronic wounds requires interactive dressings that not only meet basic biological criteria, of biocompatibility, but also offer additional functionalities such as antioxidant and antibacterial properties. In this study, three novel multifunctional nanofibrous membranes based on EPS, an α-glucan exopolysaccharide produced by <em>Lacticaseibacillus rhamnosus</em> P14, blended with PEO as a co-polymer were successfully developed using electrospinning. The membranes incorporated Cu or Ag-doped bioactive glass (BG) nanoparticles, to enhance their functionalities. The structural and thermal properties of the electrospun membranes were characterized using FT-IR, TGA, and DSC analysis. In addition, the surface morphology, fiber size, and porosity were examined by SEM analysis. Additionally, their biological properties, including antioxidant and antibacterial activities, were thoroughly investigated. SEM confirmed the effective electrospinning of the EPS-PEO and EPS-PEO-BG blends from aqueous solutions using optimized process parameters, resulting in the successful incorporation of the BG nanoparticles and uniform fibers with average diameter ranging from 270 to 352 nm. Moreover, DPPH RSA and FRAP assays showed a significant antioxidant capacity for all prepared membranes which is attributed to the EPS component. Moreover, the antibacterial activity revealed a notable inhibition against <em>E. coli</em> and <em>S. aureus</em> after 24 h exposure to the composite membranes. This work presents a novel synergistic approach to developing multifunctional wound dressing by combining the antioxidant properties of EPS, the antibacterial activity of ion-doped bioactive glass nanoparticles, and structural benefits of electrospinning.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125594"},"PeriodicalIF":5.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834603","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":"Chitosan-aloe vera scaffolds with tuned extracellular vesicles and histatin-5 display osteogenic and anti-biofilm activities","authors":"Patricia García-García ,&nbsp;Carmen Évora ,&nbsp;Araceli Delgado ,&nbsp;Patricia Diaz-Rodriguez","doi":"10.1016/j.ijpharm.2025.125592","DOIUrl":"10.1016/j.ijpharm.2025.125592","url":null,"abstract":"<div><div>The use of extracellular vesicles (EVs) has garnered significant attention as an alternative to cell-based therapies due to their stability and biocompatibility. In this study, we stimulated mesenchymal stem cells (MSCs) with therapeutic agents affecting the bone regenerative cascade, including bone morphogenetic protein 2 (BMP-2), stromal-derived factor (SDF-1), interleukin 4 (IL-4), alendronate (ALD) and osteogenic differentiation media to obtain osteogenic EVs. The tuned EVs were tested on MSCs and fibroblasts, selecting EVs-BMP-2 as suitable systems. Chitosan-aloe vera (AV) scaffolds were designed to allow for the loading and release of these EVs while leveraging the antibacterial and anti-inflammatory properties of AV. To enhance the dual effect on regeneration and antibacterial activity, poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating Histatin 5 (Hist-5) were incorporated to the scaffolds. Hist-5 encapsulation was successful, and effectively prevented <em>Staphylococcus aureus</em> biofilm formation on the scaffolds surface. The optimized chitosan-AV scaffolds loaded with EVs-BMP-2 promoted MSCs adhesion and proliferation and exhibited a 2-fold increase in osteogenic differentiation compared to chitosan scaffolds. This study demonstrates the successful combination of bioengineered EVs and Hist-5-loaded microspheres within a chitosan-AV scaffold, providing a promising dual approach for enhancing bone regeneration while reducing the risk of infection. These systems show potential as effective implants for bone fractures, offering both antibacterial and regenerative capabilities.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125592"},"PeriodicalIF":5.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838142","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":"State-of-the-art surfactants as biomedical game changers: unlocking their potential in drug delivery, diagnostics, and tissue engineering","authors":"Karuppiah Nagaraj ,&nbsp;S. Kamalesu","doi":"10.1016/j.ijpharm.2025.125590","DOIUrl":"10.1016/j.ijpharm.2025.125590","url":null,"abstract":"<div><div>This review presents a comprehensive analysis of surfactant-based medicinal formulations, highlighting both their advantages and disadvantages. Surfactants enhance drug solubility, enhance targeted delivery, and facilitate controlled release of drugs. Their antimicrobial action is a result of their ability to disrupt microbial membranes, and their application in the delivery of genes and proteins involves stabilizing lipid nanoparticles for messenger ribonucleic acid (mRNA) vaccines and clustered regularly interspaced short palindromic repeats (CRISPR). Surfactants also assist in biomedical imaging and theranostics by enhancing magnetic resonance imaging (MRI) contrast, fluorescence bioimaging, and cancer diagnosis. In tissue engineering, they assist in the manufacturing of scaffolds and coatings of biomaterials. In spite of their broad application, cytotoxicity concerns, environmental impact, and regulatory constraints bar clinical use. Biodegradable biosurfactants, stimuli-responsive intelligent surfactants, and AI-driven formulation design are areas that future studies can focus on to enhance safety and effectiveness in current healthcare applications.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125590"},"PeriodicalIF":5.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838140","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":"3D-printed microneedles loaded with madecassoside for periodontal soft tissue regeneration","authors":"Yiyao He ,&nbsp;Dawei He ,&nbsp;Song Ren ,&nbsp;Lin Fan ,&nbsp;Lin Wang ,&nbsp;Jiang Sun","doi":"10.1016/j.ijpharm.2025.125569","DOIUrl":"10.1016/j.ijpharm.2025.125569","url":null,"abstract":"<div><div>Gingival recession is a common clinical concern. While surgical intervention remains the conventional approach for periodontal soft tissue regeneration, it is often associated with trauma. Recent advancements emphasize minimally invasive and effective alternatives. This study developed a hydrogel microneedle (MN) patch loaded with madecassoside using 3D printing technology to promote periodontal soft tissue regeneration. The PEGDA hydrogel-based MN patch exhibited excellent mechanical properties and biocompatibility, enabling effective skin penetration. <em>In vitro</em> studies demonstrated that madecassoside at specific concentrations enhanced gingival fibroblast proliferation and type I collagen expression. Animal experiments further confirmed that microneedles containing madecassoside effectively promoted periodontal soft tissue regeneration in rabbits. These findings demonstrate the potential of 3D-printed hydrogel microneedles as a promising approach for periodontal soft tissue regeneration, supporting both tissue repair and collagen synthesis.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125569"},"PeriodicalIF":5.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838143","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}