International Journal of Pharmaceutics: X最新文献

{"title":"Bone-seeking nanomaterials for rebalancing bone remodeling in osteoporosis","authors":"Fei Wang ,&nbsp;Feng Liang ,&nbsp;Xiaonan Zhou ,&nbsp;Yuanyuan Ding ,&nbsp;Mingzhe Wu ,&nbsp;Nan Li ,&nbsp;Fei Wang ,&nbsp;Wei Yan","doi":"10.1016/j.ijpx.2026.100578","DOIUrl":"10.1016/j.ijpx.2026.100578","url":null,"abstract":"<div><div>Osteoporosis is a prevalent skeletal disorder characterized by reduced bone mass and microarchitectural deterioration, primarily resulting from an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Although current anti-osteoporosis drugs can slow bone loss or stimulate bone formation, their clinical effectiveness is often limited by poor bone specificity, systemic side effects, and insufficient restoration of physiological bone remodeling. Recently, bone-seeking nanomaterials have emerged as a promising strategy to enhance therapeutic precision in osteoporosis. By integrating bone-targeting ligands with engineered nanocarriers, these systems enable preferential accumulation in mineralized tissues and improve the local delivery of therapeutic agents. In addition to conventional anti-resorptive and anabolic drugs, nanoplatforms have been developed to deliver nucleic acids, growth factors, and immunomodulatory molecules that regulate the complex cellular networks governing bone remodeling. This review summarizes recent advances in bone-targeted nanomaterial design, discusses their roles in modulating osteoclasts, osteoblasts, osteocytes, and osteoimmune interactions, and highlights key challenges and future opportunities for the clinical translation of nanomedicine in osteoporosis therapy. Distinct from prior reviews that often emphasize nanocarrier composition or individual payload classes, this review is organized around the concept of rebalancing bone remodeling and integrates osteoclast, osteoblast, osteocyte, and osteoimmune regulation with emerging translational considerations.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100578"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148241075","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":"Design of immediate release combination preparation containing alkalizer and lansoprazole for mechanistic understanding of enhanced gastric stability, pharmacokinetics, and intragastric pH variability in healthy human subjects.","authors":"Il-Ki Hong, Dinh Hoai Nam, Youngju Jeong, Jun-Bom Park, Chulhun Park, Beom-Jin Lee","doi":"10.1016/j.ijpx.2026.100579","DOIUrl":"10.1016/j.ijpx.2026.100579","url":null,"abstract":"<p><p>We investigated the microenvironmental pH (pH_M)-modulating mechanism and intermolecular interaction of alkalizers and their impact on the aqueous stability, release profiles of drugs and alkalizers, pharmacokinetics, and intragastric pH variability in 46 healthy human subjects of lansoprazole (LAN), an acid-labile model drug. Preliminary screening of five alkalizers (CaCO₃, MgO, NaHCO₃, meglumine, and L-arginine) in LAN-loaded wet granules under simulated gastric fluid demonstrated that calcium carbonate (CaCO₃) appeared to be the best stabilizing agent for LAN in a dose-dependent manner according to solution pH changes and drug contents. Immediate-release fixed-dose combination tablets (IFT) containing LAN and CaCO₃ were prepared via a dual granulation process using a fluidized bed dryer (FBD) and/or a high shear mixer (HSM). Unlike the commercial enteric-coated granule-loaded Lanston® capsule, IFT released LAN and CaCO₃ simultaneously, achieving over 90% drug release within 30 min while maintaining its aqueous stability in pH 1.2 gastric fluid via the acid-neutralizing capacity of simultaneously released CaCO₃. The increased modulation of pH_M and the intermolecular complex of LAN with calcium ions are crucial for stabilizing LAN under low pH conditions. The optimal IFT formulation demonstrated long-term stability for 3 years, maintaining drug content and dissolution rates while liberating impurities (<0.2%) within regulatory guidelines. IFT demonstrated bioequivalence with the commercial enteric-coated Lanston® capsule with decreased \"time to reach the maximum plasma concentration\" and displayed superior intragastric pH control, maintaining pH above 4 for a longer duration over 24 h in a cross-over design in 46 healthy human subjects. The current novel IFT containing acid-labile LAN and CaCO₃ can be used to substitute current enteric-coated LAN tablets for the immediate release and rapid onset of LAN without chemical degradation in the gastric fluid.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"100579"},"PeriodicalIF":7.9,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13266252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resiquimod-loaded magnetic nanoparticles reprogram macrophages and induce oxidative cytotoxicity against triple-negative breast cancer cells.","authors":"Kamonlatth Rodponthukwaji, Ladawan Khowawisetsut, Nathachit Limjunyawong, Sith Sathornsumetee, Chatchawan Srisawat, Numpon Insin, Tam Nguyen, Primana Punnakitikashem","doi":"10.1016/j.ijpx.2026.100577","DOIUrl":"10.1016/j.ijpx.2026.100577","url":null,"abstract":"<p><p>The development of alternative cancer therapies remains a critical priority to overcome the significant adverse effects associated with conventional chemotherapy. Accordingly, innovative strategies are required to mitigate chemotherapy-induced toxicity. Among these, reprogramming the immunosuppressive tumor microenvironment into an immunostimulatory state has emerged as a promising approach; however, single-modality approaches often underperform. In this work, we engineered resiquimod (<i>R</i>848)-loaded carboxymethyl dextran-coated magnetic nanoparticles (MD-R848) to repolarize M2 macrophages toward an M1 phenotype and to exert direct cytotoxicity against triple-negative breast cancer cells. Nanoparticle physicochemical properties were characterized by dynamic light scattering, X-ray powder diffraction, Fourier-transform infrared spectroscopy, ultraviolet-visible spectrophotometry, and inductively coupled plasma optical emission spectrometry. MD-R848 increased the expression of the M1 surface marker CD80 and reduced the expression of the M2 marker CD206 in macrophages, as determined by flow cytometry. This phenotypic shift was accompanied by increased secretion of the proinflammatory cytokines TNF-α and IL-6, together with upregulation of <i>TNF</i> and <i>IL6</i> gene expression, supporting M1-like macrophage polarization. MD-R848 also decreased viability of MDA-MB-231 triple-negative breast cancer cells, likely via oxidative stress, as reactive oxygen species and malondialdehyde, a lipid peroxidation marker, increased by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) fluorescence and lipid peroxidation assays. The elevated reactive oxygen species and malondialdehyde were attributable to the magnetic nanoparticle core. In a transwell co-culture, macrophage reprogramming combined with direct tumor cytotoxicity synergistically intensified cancer cell death. Thus, MD-R848 represents a dual-function nanoplatform that couples immunomodulation with oxidative cytotoxicity, providing a mechanistic basis for improved therapeutic outcomes in cancer treatment.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"100577"},"PeriodicalIF":7.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13254843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid droplets-mediated delivery of curcumin for targeted mitochondrial photodynamic therapy.","authors":"Wen Lin, Shuni Zeng, Qiwei Chen, Zhitao Wang, Defang Ouyang, Yan Ma","doi":"10.1016/j.ijpx.2026.100576","DOIUrl":"10.1016/j.ijpx.2026.100576","url":null,"abstract":"<p><p>Lipid droplets (LDs), intracellular organelles characterized by a phospholipid monolayer shell enclosing a neutral lipid core, serve as ideal reservoirs for lipophilic drugs. By exploiting the β-oxidation pathway, lipids stored in LDs can be transported to mitochondria, enabling targeted drug delivery. Notably, by altering the culture conditions, the particle size of LDs within cells can be regulated, demonstrating their suitability for development as drug carriers. Curcumin (CUR), a natural lipophilic photosensitizer, exhibits considerable potential for applications in photodynamic therapy (PDT). We confirmed that exogenous LDs can be taken up by cells and effectively localized around mitochondria. Then we exploited LDs as drug carriers to develop curcumin-loaded LDs (CUR-LDs) that capitalize on the intrinsic interplay between LDs and mitochondria to enable targeted mitochondrial delivery for photodynamic therapy. In vitro, CUR-LDs irradiated with 450 nm light (100 mW/cm², 5 min) significantly increased intracellular reactive oxygen species (ROS) levels (5.2-fold), together with inactivation of mitochondrial cytochrome oxidase and reduced mitochondrial membrane potential (JC-1 red/green ratio: from 26.50 ± 4.81 to 1.76 ± 0.04), and ultimately promoted apoptotic cell death. These results highlight LDs as promising mitochondria-targeted drug carriers and demonstrate an effective curcumin formulation with potential applications in cancer therapy.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"100576"},"PeriodicalIF":7.9,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13235511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148198813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced azelaic acid hyalubilosome-loaded microneedles for potent anti-inflammatory, antioxidant, and antimicrobial for Acne treatment by up-regulation of Nrf2/HO-1 signaling pathway.","authors":"Sammar Fathy Elhabal, Mohamed Fathi Mohamed Elrefai, Fatma E Hassan, Nahla Sameh Tolba, Rania Mostafa Abd El Galil, Suzan Awad AbdelGhany Morsy, Shady Allam, Amr M Emam, Hanaa Wanas, Marian Sobhy Azer, Mona Mohamed Ahmed, Hoda Ahmed Abdelmoneim, Marwa Fady, Ahmed Mohsen Elsaid Hamdan","doi":"10.1016/j.ijpx.2026.100570","DOIUrl":"10.1016/j.ijpx.2026.100570","url":null,"abstract":"<p><p>Acne vulgaris is a multifactorial inflammatory skin disorder in which the clinical utility of azelaic acid (AZA) is limited by poor aqueous solubility and inadequate skin permeation. This study developed AZA-loaded hyalubilosomes (AZA-HBs) integrated into dissolving PVA/PVP-chitosan microneedles (MNs) to improve dermal delivery and anti-acne efficacy. AZA-HBs formulations were developed using Design-Expert® software to study the effects of hyaluronic acid and bile salt amount, optimized via I-optimal design, and incorporated into dissolving MNs. The optimized AZA-HBs showed high entrapment efficiency (87.0 ± 0.55%), nanosized vesicles (170 ± 0.72 nm), narrow dispersity (PDI 0.33 ± 0.01), and good colloidal stability (zeta potential -29 ± 0.28 mV). The selected MN formulation exhibited excellent drug loading (95.3 ± 1.2%), strong mechanical performance with only (11.0 ± 1.0%) height reduction, and efficient insertion. The hybrid platform provided sustained AZA release, reaching (94-95%) over 48 h, and increased ex vivo skin permeation by (6.3-fold). It also improved cytocompatibility in HaCaT cells, whereas free AZA caused complete cell loss at the highest tested concentration. Moreover, the formulation enhanced antimicrobial potency (MICs of 6.25 μg/mL against <i>S. epidermidis</i> and 12.5 μg/mL against <i>S. aureus</i>) and eradicated (78%) of the biofilm. In vivo, AZA-HBs/MNs produced the strongest anti-acne effect, markedly reducing ear inflammation, suppressing TNF-α, IL-1β, IL-6, and TLR4, modulating Nrf2/HO-1/MYD88 signaling, and restoring normal histological and EGF immunohistochemical features. AZA-HBs-loaded dissolving PVA/PVP-chitosan microneedles offer sustained release, superior penetration, strong antimicrobial/antibiofilm activity, and significant anti-acne efficacy for topical AZA delivery.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"100570"},"PeriodicalIF":7.9,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13235371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148198838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for the existence of the <i>Magenstrasse</i> and the <i>Darmstrasse</i> when ingesting a caloric solution after a solid meal: A MRI study.","authors":"Linus Großmann, Lydia Neubauer, Miriam Lisanne Seidel, Rebecca Kessler, Michael Grimm, Werner Weitschies","doi":"10.1016/j.ijpx.2026.100573","DOIUrl":"10.1016/j.ijpx.2026.100573","url":null,"abstract":"<p><p>Magnetic resonance imaging was used to investigate gastric emptying and small-intestinal distribution of a manganese-labeled 10.6% glucose solution in a randomized crossover study in 12 healthy volunteers under fasted and postprandial conditions after ingestion of a solid light meal. Following the ingestion of 240 mL of the test solution (100 kcal), manganese contrast appeared rapidly in the small intestine and reached distal regions within approximately 20 min in 9 out of 12 subjects, irrespective of the prandial state. Contacted small-intestinal length and small-intestinal distribution increased continuously during the early phase and plateaued thereafter, closely paralleling gastric emptying of the solution. While absolute intestinal contact lengths were lower under postprandial conditions, normalized spreading showed comparable temporal profiles in fasted and fed states, indicating similar distribution mechanisms. Although distribution was slower than previously reported for water, the spatial extent of intestinal spreading was largely preserved in the caloric vehicle. These findings demonstrate that the <i>Magenstrasse</i> and <i>Darmstrasse</i> are not restricted to non-caloric liquids but also govern the rapid luminal distribution of substances dissolved in caloric solutions, largely independent of prandial state, with relevant implications for oral drug delivery and food-effect interpretation.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"100573"},"PeriodicalIF":7.9,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13235519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148198801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of a temperature responsive semi-inter-penetrating polymer network of poly (diethyl acrylamide)-xanthan gum enriched with umbilical cord blood serum for wound healing.","authors":"Reyhaneh Ranjbar, Jaleh Varshosaz, Fatemeh Baneshi, Mohsen Minaiyan, Mina Mirian, Majid Tabbakhian, Salar Nasr Esfahani","doi":"10.1016/j.ijpx.2026.100571","DOIUrl":"10.1016/j.ijpx.2026.100571","url":null,"abstract":"<p><p>Human umbilical cord blood serum (UCBS) represents a potential reservoir of growth factors, neurotrophic factors, and cytokines, with anti-inflammatory properties. This study aimed to synthesize a temperature sensitive interpenetrating polymer network (semi-IPN) of diethyl acrylamide and xanthan gum enriched with UCBS for damaged skin tissue. The advantages of 3D IPN hydrogel are enhanced material-exchange, biocompatibility, and mechanical properties adjustability. The semi-IPN containing 1% xanthan gum exhibited the lower critical solution temperature of about 32 °C. 70% of the loaded UCBS in hydrogel was released within 24 h. The semi-IPN dramatically promoted cells proliferation and adhesion. 99% wound closure happened by the hydrogel loaded UCBS. Histological and immunohistochemical analyses indicated that the gel reduced inflammation, downregulated surface CD31 markers, increased collagen density, and accelerated re-epithelialization in the healed tissue, suggesting improved tissue regeneration. These findings highlight the strong potential of semi-IPN diethyl acrylamide-xanthan gum hydrogel dressing for effective management of open wounds.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"100571"},"PeriodicalIF":7.9,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13226223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to 'Biomimetic nanotherapy for <i>P. gingivalis</i>-infected oral squamous cell carcinoma: Photothermal therapy and immunoactivation via precise intracellular bacterial elimination' [International Journal of Pharmaceutics: X 10 (2025) 100438].","authors":"Zihan Dai, Qiaoxin Li, Longxuan Guo, Kaijing Zhong, Jing Cheng, Xiuhong Weng, Bo Cheng","doi":"10.1016/j.ijpx.2026.100501","DOIUrl":"https://doi.org/10.1016/j.ijpx.2026.100501","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.ijpx.2025.100438.].</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"100501"},"PeriodicalIF":7.9,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Application of ultrasound and ultrasound-responsive materials in wounds: A systematic review\" [International Journal of Pharmaceutics: X 11 (2026) 100485].","authors":"Jialei Luo, Liwan Song, Xinyi Yan, Xiaolu Ma, Jianqing Gao, Ying Luo, Gaoyi Yang","doi":"10.1016/j.ijpx.2026.100500","DOIUrl":"https://doi.org/10.1016/j.ijpx.2026.100500","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.ijpx.2026.100485.].</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"100500"},"PeriodicalIF":7.9,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Development and evaluation of clotrimazole microemulsions for topical application: Effects of HLB value of surfactant mixture and cosurfactant type on formulation design\" [International Journal of Pharmaceutics: X Volume 11, (June 2026), 100469].","authors":"Chih-Wun Fang, Yu-Wen Lin, I-Hui Chiu, Pao-Chu Wu","doi":"10.1016/j.ijpx.2026.100490","DOIUrl":"https://doi.org/10.1016/j.ijpx.2026.100490","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.ijpx.2025.100469.].</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"100490"},"PeriodicalIF":7.9,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}