International Journal of Pharmaceutics: X最新文献

{"title":"In vitro, ex vivo, and in vivo evaluation of ophthalmic ointments containing dexamethasone and tobramycin","authors":"Catheleeya Mekjaruskul ,&nbsp;Andre O'Reilly Beringhs ,&nbsp;Tuo Meng ,&nbsp;Aji Alex Moothedathu Raynold ,&nbsp;Qingguo Xu ,&nbsp;Matthew Halquist ,&nbsp;Bin Qin ,&nbsp;Yan Wang ,&nbsp;Xiuling Lu","doi":"10.1016/j.ijpx.2025.100476","DOIUrl":"10.1016/j.ijpx.2025.100476","url":null,"abstract":"<div><div>This investigation compares <em>in vitro</em> release, <em>ex vivo</em> release and permeation, and <em>in vivo</em> ocular pharmacokinetics to render biologically informed evaluations of ophthalmic semi-solid drug products containing dexamethasone (hydrophobic) and tobramycin (hydrophilic). Both drugs were formulated with three petrolatum matrices (IGI® 320 A, IGI® 386, or Spectrum®) with distinct rheological character and benchmarked against the reference listed drug, Tobradex®. Temperature-sweep rheology revealed that IGI® 386 most closely reproduced the viscoelastic profile of the reference product. USP Apparatus I release testing with surfactant-free medium provided maximal discrimination for dexamethasone (Tobradex® &gt; IGI® 320 A &gt; IGI® 386 &gt; Spectrum®), and rank-order release rates correlated strongly with <em>ex vivo</em> corneal permeation and <em>in vivo</em> corneal exposure. In contrast, tobramycin required a polysorbate-containing medium to resolve formulation differences <em>in vitro</em>, yet those differences did not persist <em>ex vivo</em> or <em>in vivo</em>, consistent with its rapid dissolution and diffusion, which attenuate matrix effects. The data demonstrate that drug solubility dictates the choice of biorelevant release conditions in petrolatum-based ophthalmic ointments: surfactant-free media capture formulation-dependent release for hydrophobic actives, whereas hydrophilic actives may yield artifactual discrimination when surfactant is present. However, formulations indistinguishable <em>in vitro</em> were typically similar in their <em>in vivo</em> ocular pharmacokinetics. By integrating tiered models, the framework enhances understanding of critical quality attributes, supports regulatory decision-making, and may help reduce reliance on animal studies, thereby expediting the development of therapeutically equivalent generic ophthalmic ointments.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100476"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921833","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":"Double action of HPMCAS as a dry binder and precipitation inhibitor in ASD tablet formulations of nifedipine prepared by hot-melt extrusion","authors":"David S. Nakhla ,&nbsp;Saurabh M Mishra ,&nbsp;Christian Lübbert ,&nbsp;Luis Mejia ,&nbsp;Kess Agatovure ,&nbsp;Andreas Sauer","doi":"10.1016/j.ijpx.2025.100475","DOIUrl":"10.1016/j.ijpx.2025.100475","url":null,"abstract":"<div><div>Poor tablet hardness and drug re-crystallization are two common challenges of amorphous solid dispersion (ASD) formulations prepared with hot-melt extrusion (HME). In the present study, we investigated the double action of hypromellose acetate succinate (HPMCAS) as a dry binder and precipitation inhibitor when externally added to high ASD load (65 %) tablets of nifedipine (NIF). Binary ASDs of NIF were prepared using either HPMCAS or copovidone (Kollidon® VA 64, PVP-VA64) as carrier polymers. Pre-dissolving HPMCAS (AS-HF) in the dissolution medium inhibited the drug precipitation and prolonged its supersaturation state at 12.5 wt % or 100 wt % relative to NIF content in ASDs prepared with either HPMCAS (1: 2, drug: polymer), or PVP-VA64 (1: 6, drug: polymer), respectively. In contrast, pre-dissolving hydroxypropyl cellulose (Klucel™, HPC-EXF) or PVP-VA64, did not prevent the drug re-crystallization. The external addition of AS-HF (5 % <em>w</em>/w) to the ASD tablets of NIF: HPMCAS (1: 2) improved the tabletability, compressibility and compactibility of the blend, resulting in tablets with good tensile strength (1.9 MPa) vs 1.5 MPa or 0.8 MPa with either HPC-EXF (5 % w/w) or PVP-VA64 (5 % w/w), respectively. The results from this study demonstrate, for the first time, the dual function of HPMCAS (AS-HF) as a dry binder and precipitation inhibitor in high ASD load tablets, independent of the carrier polymer. This can potentially reduce the pill burden and improve the drug bioavailability in ASD tablet formulations.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100475"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034576","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":"Punicic acid ethyl ester, a superior absorption-enhancer over pomegranate seed oil, dramatically improves quercetin bioavailability via strong interaction and rapid lipolysis","authors":"Yutong Ding ,&nbsp;Jiayi Gong ,&nbsp;Ping Yang ,&nbsp;Zhengxi Zhao ,&nbsp;Zhenglu Jiang ,&nbsp;Xinru Yang ,&nbsp;Meisha Xu ,&nbsp;Xiaoqiang Guo ,&nbsp;Yun Yan ,&nbsp;Qian Yao","doi":"10.1016/j.ijpx.2026.100499","DOIUrl":"10.1016/j.ijpx.2026.100499","url":null,"abstract":"<div><div>Low oral bioavailability remains a major challenge for drug delivery. Fatty acids (FAs) and vegetable oils have attracted great interest as absorption enhancers due to their excellent compatibility. However, the difference in absorption-enhancing efficiency of various FA chemical forms and the underlying mechanisms remain unclear. In vegetable oils, FAs are confined within rigid triglyceride structures, whereas free FAs or their monoesters possess flexible carbon chains. We hypothesize that such molecular flexibility facilitates stronger drug interactions, resulting in greater absorption-enhancing capacity for FAs or their monoesters compared with parent oils. To validate this, punicic acid (PA) was isolated from pomegranate seed oil (PSO) and converted into its ethyl ester (PAEE). Employing quercetin (QU) as the model drug and oleic acid (OA) as a control, we systematically evaluated the effect of PAEE, PSO, OA, and their nanoemulsions (NE) on QU physiochemical characteristics. <em>In vitro</em>, the antibacterial activity followed the order of QU-PAEE &gt; QU-PSO &gt; QU-OA &gt; QU. Among the oils, PAEE showed strongest protection on QU in gastrointestinal fluid, the greatest interaction with QU, and significantly faster lipolysis than PSO. NE formulations further amplified these effects. <em>In vivo</em>, PAEE, PSO, and OA increased QU oral bioavailability by 4.57-, 3.49-, and 3.07- fold, respectively, whereas their NE achieved 20.66-, 6.42-, and 6.19- fold increases. This study identifies PAEE as a highly efficient and safe absorption-enhancer and, more importantly, demonstrates that FA monoesters present markedly stronger absorption-enhancing efficiency than their parent oils, providing new insights for the design of lipid-based drug carriers.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100499"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165172","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":"Oxygen-sparing photodynamic therapy via dissolving microneedles for rheumatoid arthritis","authors":"Lijie Zheng ,&nbsp;Yingying Li ,&nbsp;Xun Gu ,&nbsp;Xinao Chang ,&nbsp;Man Jiang ,&nbsp;Wenjun Shao ,&nbsp;Hanqing Zhao ,&nbsp;Fangyuan Chen ,&nbsp;Tao Ma ,&nbsp;Qingqing Wang","doi":"10.1016/j.ijpx.2025.100481","DOIUrl":"10.1016/j.ijpx.2025.100481","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation, which leads to significant morbidity and disability. Although current therapies offer benefits to some patients, they often fail to fully address the intricate pathophysiology of RA, particularly the inflammatory proliferation and hypoxic microenvironment in synovial tissue. Herein, we propose an oxygen-sparing photodynamic therapy (PDT) strategy via dissolving microneedles (DMNs), in which both the photosensitizer and glycolysis inhibitor are simultaneously loaded into the DMNs for RA treatment. The strategy integrates PDT to target and suppress synovial hyperplasia and alleviate joint inflammation and bone damage. Additionally, an oxygen-sparing strategy was employed through glycolysis inhibition to improve the hypoxic microenvironment in RA, thereby potentiating PDT, reducing inflammatory microenvironmental factors, and promoting inflammatory cell death. In vitro results demonstrated that the combination treatment significantly increased reactive oxygen species (ROS) levels by 426.15 %, reduced ATP content by 34.78 %, and induced significant death in inflammatory synovial cells, decreasing cell viability to 14.69 %. In adjuvant arthritis (AA) rats, the treatment significantly reduced paw swelling by 20.99 %, alleviated splenomegaly by 39.62 %, and improved inflammation and related pathological changes in both synovial and ankle tissues. Furthermore, the treatment significantly reduced serum levels of pro-inflammatory cytokines, indicating a broad anti-inflammatory effect. This multifaceted approach not only enhances therapeutic efficacy for RA but also provides a theoretical basis for the development of innovative treatment formulations.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100481"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921849","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":"Precision PEGylation of ZnO quantum dots enables selective intracellular killing of Uropathogenic E. coli via multimodal antibacterial mechanisms without inducing resistance","authors":"Jingqi Niu ,&nbsp;Fangyuan Du ,&nbsp;Mingxuan Zhang ,&nbsp;Beiliang Miao ,&nbsp;Yu Hong ,&nbsp;Heyujia Yu ,&nbsp;Xiaohua Liang ,&nbsp;Mengqi Gao ,&nbsp;Qifan Chen ,&nbsp;Shiwei Liu ,&nbsp;Baoshan Liu ,&nbsp;Hongwei Xin ,&nbsp;Zeliang Chen","doi":"10.1016/j.ijpx.2025.100479","DOIUrl":"10.1016/j.ijpx.2025.100479","url":null,"abstract":"<div><div>The intracellular persistence and biofilm-forming capacity of uropathogenic <em>Escherichia coli</em> (UPEC) are major contributors to urinary tract infections (UTIs) recurrence and antibiotic failure. Here, we report a precisely engineered nanotherapeutic based on ZnO quantum dots (QDs) surface-functionalized with low-molecular-weight polyethylene glycol (PEG200), designed to enhance biocompatibility while preserving potent antibacterial activity. The optimized ZnO@PEG200 QDs exhibited excellent aqueous dispersibility, minimal cytotoxicity, and broad-spectrum efficacy against both drug-sensitive and multidrug-resistant <em>Escherichia coli</em> strains. Mechanistic studies revealed that the QDs exerted multimodal bactericidal effects, including Zn²⁺ ion release, membrane destabilization, intracellular reactive oxygen species (ROS) generation, genomic DNA fragmentation, and transcriptional repression of key virulence genes such as papG, FimH, and FliC. Notably, ZnO@PEG200 QDs disrupted bacterial motility and eradicated established biofilms even at sub-inhibitory concentrations. Long-term passaging assays demonstrated that sub-MIC exposure to ZnO@PEG200 QDs did not induce resistance development. In vivo, the QDs preferentially accumulated in the bladder and kidneys, significantly reduced intracellular bacterial burden, suppressed inflammatory cytokine expression, and promoted tissue repair in a murine UTIs model. Collectively, this work establishes ZnO@PEG200 QDs as a safe and effective nanoplatform for precision antimicrobial therapy, offering a resistance-free strategy for the treatment of intracellular and biofilm-associated bacterial infections.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100479"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921850","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":"HPMA polymers as functional excipients in dermal nanoformulations of imiquimod","authors":"Eliška Kurfiřtová ,&nbsp;Stanislav Chvíla ,&nbsp;Nikola Strnádková ,&nbsp;Vendula Janoušková ,&nbsp;Petr Chytil ,&nbsp;Tomáš Etrych ,&nbsp;Jarmila Zbytovská","doi":"10.1016/j.ijpx.2026.100486","DOIUrl":"10.1016/j.ijpx.2026.100486","url":null,"abstract":"<div><div>A key challenge in topical drug delivery is the inherently low bioavailability of many active compounds within skin tissue. Here, we present the first comprehensive study investigating the impact of biocompatible hydrophilic polymers based on <em>N</em>-(2-hydroxypropyl)methacrylamide (p(HPMA)) on skin barrier properties and its potential to enhance drug permeation. Using imiquimod (IMQ), a model compound known for its poor dermal delivery, we demonstrate that p(HPMA) can significantly influence transport across the skin. To enhance the dermal delivery of IMQ, we investigated three p(HPMA) polymers of varying molecular sizes (5, 20, 80 kg/mol) with very low dispersity. Our initial focus was on the p(HPMA) interaction with the skin barrier, specifically within the <em>stratum corneum</em> (SC), which was studied by confocal microscopy. Results revealed that p(HPMA) can penetrate into deeper skin layers, with this ability inversely correlated with their molecular weight. FTIR analysis confirmed that the polymers increase SC hydration without disrupting lipid organization. As demonstrated by the <em>ex vivo</em> skin permeation study, the smallest p(HPMA) polymer (5 kg/mol) produced the strongest enhancement effect on IMQ delivery into skin tissue. Relative to p(HPMA)-free controls, IMQ accumulation increased by 90% from the conventional suspension and by 10% and 50% from the nanoemulsion and nanocrystal formulations, respectively. These findings substantiate the role of p(HPMA) as an effective skin-penetration enhancer and support its further investigation for optimizing topical drug-delivery systems.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100486"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978486","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":"Liposomal antimicrobials in the fight against bacterial and fungal pathogens: Clinical successes and development challenges","authors":"Hussein T. Kenaan ,&nbsp;Ross M. Duncan ,&nbsp;Wafa T. Al-Jamal ,&nbsp;David S. Jones ,&nbsp;Gavin P. Andrews ,&nbsp;Brendan Gilmore ,&nbsp;Vanessa Yardley ,&nbsp;Nicola Farrington ,&nbsp;Katharine E. Stott ,&nbsp;David Lawrence ,&nbsp;Joseph N. Jarvis ,&nbsp;Thomas S. Harrison ,&nbsp;Stephen Robinson ,&nbsp;Isabela Ribeiro ,&nbsp;William Hope ,&nbsp;Yiwei Tian","doi":"10.1016/j.ijpx.2025.100478","DOIUrl":"10.1016/j.ijpx.2025.100478","url":null,"abstract":"<div><div>Bacterial, fungal, and protozoan infections pose a rapidly escalating threat to global health, exacerbated by the rise in antimicrobial resistance. Current therapies against microbial pathogens are limited by high systemic toxicity and poor drug solubility. Liposomal formulations (spherical vesicles composed of lipid bilayers) have demonstrated remarkable clinical potential in addressing these concerns, as evidenced by the marketed products AmBisome® and Arikayce®. These products, which deliver amphotericin B via parenteral injection and amikacin via inhalation, exemplify how liposomes effectively mitigate drug-associated toxicity, enhance therapeutic efficacy, and overcome the biological barriers inherent to infection sites, including complex microbial biofilms, mucosal interfaces, or the blood–brain barrier. Complementary insights from anticancer research indicate that strategic manipulation of liposomal composition and structure can enhance their therapeutic potential. Adjustments in lipid charge, fluidity, and PEGylation, in particular, highlight their versatility and broad applicability for antimicrobial drug delivery. Liposomal antimicrobials can modulate pharmacokinetic profiles, achieve targeted release at sites of infection, and increase local drug concentrations, which are key advantages over conventional treatments. Despite these therapeutic advances, successful clinical translation and widespread adoption of liposomal antimicrobials remain highly dependent on overcoming existing technological and manufacturing challenges. This review emphasises the need for a paradigm shift within liposomal antimicrobial development, encouraging progression from initial research and development toward scalable, reproducible, and economically viable commercial manufacturing platforms. This transition is essential not only for ensuring the global accessibility and affordability of existing therapies but also for expanding the development of clinically relevant liposomal antimicrobial nanomedicines.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100478"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977958","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":"Hydrogel-encapsulated antioxidant nanotherapeutics against age-related macular degeneration (AMD) oxidative damage","authors":"Jiemeng Xu ,&nbsp;Taoyang Cai ,&nbsp;Jing Li ,&nbsp;Shangjie Ge-Zhang ,&nbsp;Zhouzhou Jiang ,&nbsp;Mingfang Cao","doi":"10.1016/j.ijpx.2025.100477","DOIUrl":"10.1016/j.ijpx.2025.100477","url":null,"abstract":"<div><div>Age-related macular degeneration (AMD) is still the main cause of irreversible vision loss, and the current intravitreal injections is limited by frequent administration and short retinal residence time. This review summarizes the latest progress of hydrogel-nanocarrier hybrid systems, aiming at prolonging ophthalmic drug delivery and supporting retinal tissue. We summarized the pathogenesis of AMD, focusing on oxidative stress and degeneration of retinal pigment epithelium (RPE), and investigated inorganic and organic nano-platforms endowed with antioxidant, anti-inflammatory and anti-angiogenesis functions. The design strategy of embedding nanoparticles into injectable or stimulus-responsive hydrogels is discussed. However, challenges remain, including long-term biocompatibility, inflammatory response to degradation products and potential tissue accumulation. Finally, it is emphasized to accelerate clinical translation through comprehensive long-term in vivo safety evaluation, quantitative optimization of release kinetics, standardized evaluation scheme and development of extensible manufacturing process. It is worth noting that this review mainly emphasizes inorganic nanoparticles and extracellular vesicles, but does not discuss other mature organic nanocarriers in detail. These carriers have been widely studied and emphasized by many other reviews.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100477"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921973","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":"Gold-incorporated hyaluronic acid nanoparticles enhance ablative radiotherapy efficacy in lung cancer","authors":"Jenny Ling-Yu Chen ,&nbsp;Shu-Jyuan Yang ,&nbsp;Li-Cheng Lin ,&nbsp;Chun-Kai Pan ,&nbsp;Ching-Yi Tsai ,&nbsp;Yu-Sen Huang ,&nbsp;Ke-Cheng Chen ,&nbsp;Ming-Jium Shieh ,&nbsp;Yu-Li Lin","doi":"10.1016/j.ijpx.2025.100480","DOIUrl":"10.1016/j.ijpx.2025.100480","url":null,"abstract":"<div><div>We aimed to investigate the utility of Au-incorporated hyaluronic acid nanoparticles (Au/HA NPs) for improving the therapeutic efficacy of ablative radiotherapy (RT) for tumor control and microenvironment remodeling. HA-functionalized NPs exhibited uniform size, stability, and efficient SN38 encapsulation. Au incorporation increased NP diameter and reduced surface charge while remaining stable. HA and Au/HA NPs were efficiently internalized by lung cancer cells, with free HA pretreatment suppressing internalization. Moreover, Au/HA NP internalization strongly downregulated CD44 expression in lung cancer cells, confirming CD44-mediated internalization. <em>In vitro</em>, Au/HA NPs enhanced radiation-induced G2/M phase arrest and γH2AX foci formation with increased DNA double-strand breaks. Au/HA NPs and RT induced immunogenic cell death (ICD) in lung cancer cells, characterized by elevated reactive oxygen species, increased calreticulin surface expression, and extracellular adenosine triphosphate release. Tumor control, survival, immune infiltration, and systemic effects were investigated <em>in vivo</em> using A549 xenografts and Lewis lung carcinoma synchronous flank-lung tumor models. Au/HA NPs and ablative RT decreased tumor growth, reduced lung tumor burden in non-irradiated areas, and prolonged survival. This therapeutic combination led to increased infiltration of natural killer (NK), NK T, CD8⁺ T, and dendritic cells and decreased regulatory T cells, suggesting robust immunological activation. Biodistribution studies confirmed CD44-targeted tumor-specific NP accumulation. No substantial toxicity was observed. In conclusion, Au/HA NPs and ablative RT induced ICD <em>in vivo</em>. Au/HA NPs enhanced local and systemic immunity <em>via</em> radiosensitization and ICD. This NP-assisted approach may improve RT efficacy in lung cancer.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100480"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921848","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":"Mitochondria-targeted delivery strategies for age-related diseases","authors":"Zefan Liu ,&nbsp;Pei Yang ,&nbsp;Guilin Cheng ,&nbsp;Xin Kang ,&nbsp;Lian Li ,&nbsp;Yucheng Xiang","doi":"10.1016/j.ijpx.2026.100494","DOIUrl":"10.1016/j.ijpx.2026.100494","url":null,"abstract":"<div><div>Aging is a complex progress accompanied with the progressive deterioration of physiological functions and a marked elevation in mortality risk. Among prominent aging theories, the free radical theory and the mitochondrial dysfunction hypothesis have gained significant attention. Thus, targeted delivery of therapeutic drug to mitochondria might be able to alleviate the mitochondrial dysfunction induced by reactive oxygen species. This review summarizes the possible molecular mechanisms between mitochondrial dysfunction and aging progression. Especially, the recent breakthroughs of mitochondrial-targeted delivery platforms for therapeutics against aging progress. Innovative strategies, including small molecular modification, mitochondrial targeting functional peptide guided delivery and some other strategies are discussed. Their translational potential in anti-aging interventions is evaluated. We anticipate that mitochondria-targeted anti-aging therapeutics will soon enter clinical translation, offering potential solutions to address current age-related challenges.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100494"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164023","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}