Mengjie Rui , Haidan Tang , Lianglai Gao , Yujiao Hu , Wenyan Liang , Yinfeng Li , Chunlai Feng
{"title":"pH-responsive polymeric nanoparticles for peptide delivery: Synergistic STING pathway activation enhances tumor immunotherapy","authors":"Mengjie Rui , Haidan Tang , Lianglai Gao , Yujiao Hu , Wenyan Liang , Yinfeng Li , Chunlai Feng","doi":"10.1016/j.ijpx.2025.100412","DOIUrl":"10.1016/j.ijpx.2025.100412","url":null,"abstract":"<div><div>Peptides hold great promise in tumor immunotherapy, but suffer from poor stability and short systemic circulation. To overcome these challenges, we developed a pH-responsive nanodelivery systems (P-NPs) based on the amphiphilic block polymer PEO-PC7A. In addition to its role in peptide encapsulation and protection, PEO-PC7A intrinsically acted as a stimulator of the interferon genes (STING) agonist, activating the cGAS-STING signaling pathway and remodeling the immunosuppressive tumor microenvironment. P-NPs were successfully prepared <em>via</em> a self-assembly technique, yielding nanoparticles with a uniform diameter of 91.2 ± 3.5 nm. Their pH-responsive behavior was confirmed by significant change in particle size and accelerated peptide release under acidic conditions. <em>In vitro</em>, P-NPs effectively increased the cytotoxic activity of T cells and induced higher interleukin-2 (IL-2) secretion compared to free peptide. In a 4 T1 tumor-bearing mouse model, intravenous administration of P-NPs achieved greater tumor growth inhibition and higher intratumoral interferon-γ (IFN-γ) levels than free peptide, with minimal systemic toxicity and no significant impact on body weight. Overall, our study presented a novel multifunctional peptide nanocarrier that enhanced tumor immunotherapy efficacy by concurrently improving peptide delivery and stimulating innate immunity, providing a promising foundation for the further development of innovative combination cancer immunotherapy strategies.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100412"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265189","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}
Marta Pollini, Eleonora Bianchi, Marco Ruggeri, Barbara Vigani, Silvia Rossi, Giuseppina Sandri
{"title":"Exploring bioadhesion: insight on innovative strategies to investigate bioadhesive scaffolds","authors":"Marta Pollini, Eleonora Bianchi, Marco Ruggeri, Barbara Vigani, Silvia Rossi, Giuseppina Sandri","doi":"10.1016/j.ijpx.2025.100359","DOIUrl":"10.1016/j.ijpx.2025.100359","url":null,"abstract":"<div><div>In the pharmaceutic field, materials with enhanced bioadhesive properties have been widely employed to produce scaffolds with deep interaction and adhesion to the biological surfaces, preventing them from dislocation and promoting cell homing, proliferation and growth. Parallelly, mucoadhesion has been extensively used to increase formulation retention onto the mucosal surface. This review aims to describe the most appropriate and relevant techniques to evaluate scaffolds bioadhesion and mucoadhesion for biomedical application, and more in details, in wound healing treatment. Different methods will be reviewed and described in order to provide an overview of the traditional approaches and the most innovative and recent tools. In addition, critical considerations on the variety of biological substrates that could be used will be reported to underline the different alternatives for testing bioadhesion, including <em>ex-vivo</em> and artificial options. Biomaterials, with a particular focus on bioadhesives, will be presented, as well as the mechanisms that govern bioadhesion and mucoadhesion.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100359"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687501","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}
Haiming Huang, Jiyong Peng, Zhiting Gao, Yongtong Huang, Wenyang Song, Wenhao Wu, Song Gao, Songsen Chen, Qingchun Xie, Shu Zhang, Jiu Wang
{"title":"Targeted delivery of PTX by lactoferrin-modified nanoemulsions for the treatment of glioblastoma.","authors":"Haiming Huang, Jiyong Peng, Zhiting Gao, Yongtong Huang, Wenyang Song, Wenhao Wu, Song Gao, Songsen Chen, Qingchun Xie, Shu Zhang, Jiu Wang","doi":"10.1016/j.ijpx.2025.100460","DOIUrl":"10.1016/j.ijpx.2025.100460","url":null,"abstract":"<p><p>Glioblastoma treatment is hindered by the blood-brain barrier (BBB), which limits the penetration and accumulation of chemotherapeutic agents. Paclitaxel (PTX), an effective chemotherapeutic drug, faces clinical challenges due toits poor solubility and restricted ability to traverse the BBB. Consequently, there is an urgent need for advanced drug delivery systems to facilitate the efficient and safe translocation of PTX across the BBB. In this study, PTX was encapsulated within nanoemulsions (NEs) conjugated to lactoferrin (Lf) via electrostatic interactions, followed by the optimization of its formulation. To investigate cellular uptake and BBB penetration, fluorescent dye coumarin 6 (C6) was incorporated into NEs. Uptake was evaluated in GL261 cells and BBB penetration in hCMEC/D3 cells. Further studies were conducted on the biodistribution in mice and the therapeutic efficacy in murine intracranial glioblastoma model. Characterization of PTX@Lf-NE demonstrated stability, biological safety, and favorable release properties. Notably, the fluorescence intensity of C6@Lf-NE was twice of C6@NE in one hour post-administration, and the drug uptake rate decreased with the addition of free Lf, confirming that Lf promotes the ability of NEs to traverse the BBB. In vivo distribution further revealed that Lf-NE increased brain distribution while reduced accumulation in other organs. In the glioblastoma model, it was found that the bioluminescent intensity of PTX@Lf-NE was significantly lower than that of PTX@NE on the 15th day of administration, indicating that the modification with Lf facilitated the targeted delivery of PTX and enhanced its therapeutic efficacy. This study successfully designed and developed an effective drug delivery system for glioblastoma treatment, which improves the translocation of drugs across the BBB.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"100460"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12721303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819237","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}
Ivana Ruseska , Amina Tucak-Smajić , Ivan Vidaković , Karin Kornmüller , Edina Vranić , Andreas Zimmer
{"title":"Optimizing microRNA delivery via albumin-decorated nanostructured lipid carriers","authors":"Ivana Ruseska , Amina Tucak-Smajić , Ivan Vidaković , Karin Kornmüller , Edina Vranić , Andreas Zimmer","doi":"10.1016/j.ijpx.2025.100441","DOIUrl":"10.1016/j.ijpx.2025.100441","url":null,"abstract":"<div><div>microRNA-27a is a promising candidate for miRNA mimic therapy to combat obesity, but its clinical application is hindered by enzymatic degradation and low membrane permeability. To address these challenges, we developed cationic nanostructured lipid carriers (cNLCs) via high-pressure homogenization as non-viral carriers for miRNA-27a. However, the formation of a protein corona in biologically-relevant media altered the particle size and surface charge, significantly reducing cellular uptake. To mitigate this issue, we hypothesized that coating miRNA/cNLC complexes with human serum albumin (HSA) will prevent protein corona formation and enhance cellular uptake. The HSA-coated miRNA/cNLC complexes, termed albuplexes, were characterized for particle size, zeta potential, morphology, and stability in various media. The integrity of the HSA coat was assessed using circular dichroism and UV/Vis spectroscopy. We also evaluated the biocompatibility and cellular uptake of albuplexes in 3T3-L1 cells. The biological effects of miRNA-27a on adipocyte development were analyzed through light microscopy and absorbance measurements of Oil-red-O dye in lipid droplets. Results indicated that albuplexes possess favourable physicochemical properties and enhanced stability in serum. Notably, albuplexes were rapidly taken up by 3T3-L cells via endocytosis, although 20 % HSA in the culture medium completely inhibited uptake. Furthermore, albuplexes exhibited an anti-adipogenic effect by reducing the lipid droplet accumulation, suggesting their potential as a therapeutic strategy for miRNA replacement in obesity treatment.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100441"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516616","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}
Kun Yu , Sicheng Huang , Guochun Yang , Junze Tang , Xiaoyu Zhao , Rui Pan , Hailiang Zhang , Menghan Xu , Xiaofei Li , Xin Cheng , Anguo Hou
{"title":"Multifunctional saikosaponin D-liposomes for hepatocellular carcinoma: Formulation optimization, characterization, and in vitro/in vivo evaluation","authors":"Kun Yu , Sicheng Huang , Guochun Yang , Junze Tang , Xiaoyu Zhao , Rui Pan , Hailiang Zhang , Menghan Xu , Xiaofei Li , Xin Cheng , Anguo Hou","doi":"10.1016/j.ijpx.2025.100445","DOIUrl":"10.1016/j.ijpx.2025.100445","url":null,"abstract":"<div><div>The study aimed to construct saikosaponin D (SSD)-based liposomes modified with phosphatidic acid (PA) and poloxamer 407 (P407) (termed P407-SSD-Lps), and to evaluate their tumor-targeting ability and antitumor efficacy through in vitro and in vivo experiments. The preparation process and formulation of the P407-SSD-Lps were optimized using single-factor and orthogonal experimental designs, followed by systematic characterization. Their antitumor activity and targeting specificity were assessed through in vitro experiments. Additionally, the tumor-targeting capability, therapeutic efficacy, and biocompatibility of the P407-SSD-Lps were investigated in murine orthotopic hepatocellular carcinoma transplantation models. The P407-SSD-Lps optimized through single-factor and orthogonal experiments exhibited ideal physicochemical properties. In vitro results demonstrated that the P407-SSD-Lps enhanced cell membrane permeability and promoted cellular uptake in the HepG2 cells. Additionally, they significantly inhibited the HepG2 cells proliferation and induced apoptosis. In murine orthotopic hepatocellular carcinoma transplantation models, the P407-SSD-Lps exhibited prolonged tumor accumulation and demonstrated potent antitumor efficacy with favorable biocompatibility. When delivering doxorubicin (DOX), the system not only retained high biocompatibility but also exhibited enhanced therapeutic efficacy. Employing the SSD as both a liposomal membrane stabilizer and a therapeutic agent constituted a novel expansion of “drug-excipient integration” material applications. Moreover, the SSD-based P407-SSD-Lps system functioned as a stable and efficient multifunctional liposomal delivery system, offering innovative therapeutic avenues for hepatocellular carcinoma treatment.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100445"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516735","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}
Hanaa Mabroum , Hamid Ait Said , Hamza Elbaza , Yousra Hamdan , Said Zayane , Rachid Hakkou , Sanae Ben Mkaddem , Rachid El Fatimy , Hicham Ben Youcef , Hassane Oudadesse , Hassan Noukrati , Allal Barroug
{"title":"Synergistic effects of bioactive glass and sodium alginate on the surface properties and therapeutic release of ciprofloxacin from apatite cements","authors":"Hanaa Mabroum , Hamid Ait Said , Hamza Elbaza , Yousra Hamdan , Said Zayane , Rachid Hakkou , Sanae Ben Mkaddem , Rachid El Fatimy , Hicham Ben Youcef , Hassane Oudadesse , Hassan Noukrati , Allal Barroug","doi":"10.1016/j.ijpx.2025.100401","DOIUrl":"10.1016/j.ijpx.2025.100401","url":null,"abstract":"<div><div>This work aims to investigate the effect of the incorporation of additives, including 46S6 bioactive glass (BG) and sodium alginate polymer (Alg), on the adsorption behavior, drug release kinetics, <em>in vitro</em> degradability, antibacterial activity, cytotoxicity, and inflammatory response of ciprofloxacin (Cip)-loaded reference cement (RC). Microstructural analysis revealed that the addition of BG and Alg to the reference cement composition (DCPD-CaCO<sub>3</sub>) significantly affected its specific surface area, porosity, surface charge, and the pH of the cement pastes, as well as the solubility of ciprofloxacin within the cement matrix. The adsorption and release behaviors of ciprofloxacin were examined in relation to these modified cement properties and the physicochemical characteristics of ciprofloxacin. The results revealed that the adsorption process was mainly governed by a Freundlich-type isotherm, which is characterized by a low affinity between the Cip molecules and the carrier surface. Moreover, the results of the antibiotic release showed that antibiotic release is influenced mainly by the pH and solubility of Cip. Depending on the composition of the cement, the release follows mechanisms driven by Fick's law of diffusion alone or in combination with other mechanisms. The <em>in vitro</em> biodegradation test of the prepared cements in phosphate buffer solution attested that adding BG and alginate improved the degradability of the reference cement. Moreover, the formulated cements exhibited good antibacterial activity against <em>Staphylococcus aureus</em> and <em>Escherichia coli</em>. Finally, the <em>in vitro</em> investigation revealed the non-cytotoxicity and non-inflammatory effects of the ciprofloxacin-loaded cements towards hPBMCs cells, confirming their biocompatibility.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100401"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154422","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}
Xiachan Chen , Yiming Liu , Jing Zou , Hao Chen , Hengrui Zhang , Yan Guo , Xingjie Zan
{"title":"Cell membrane-camouflaged nanomedicines for enhanced thrombolysis and blood-brain barrier penetration in ischemic stroke therapy","authors":"Xiachan Chen , Yiming Liu , Jing Zou , Hao Chen , Hengrui Zhang , Yan Guo , Xingjie Zan","doi":"10.1016/j.ijpx.2025.100404","DOIUrl":"10.1016/j.ijpx.2025.100404","url":null,"abstract":"<div><div>Thrombus-induced ischemic stroke (IS) remains a serious threat a serious health threat with limited therapeutic efficacy due to the dual challenges of precise thrombus targeting and restricted blood-brain barrier (BBB) penetration. While conventional nanocarriers, such as liposomes, micelles, and polymeric nanoparticles (NPs), demonstrate clinical potential due to their mature preparation protocols, their application is limited by poor targeting accuracy, inadequate biocompatibility, and rapid systemic clearance. In response, microenvironment-responsive biomimetic drug delivery systems based on cell membrane-camouflaged nanomedicines (CM-NMs) have emerged as a promising strategy, leveraging the pathological features of ischemic lesions for enhanced targeting and treatment. CM-NMs stand out by utilizing cell membranes to preserve innate targeting and/or BBB penetration capabilities. This approach also ensures high biocompatibility and minimizes the risk of immune clearance. This review highlights recent advances in CM-NMs for IS treatment, critically discussing three key approaches: (1) platelet membrane-camouflaged nanomedicines (PLM-NMs), which mimic platelet adhesion for thrombus-specific accumulation, (2) immune cell membrane NMs and stem cell membrane NMs, which leverage inflammatory tropism or homing mechanisms for enhanced BBB penetration, and (3) hybrid membrane NMs, which enable multi-targeting capabilities. Furthermore, we discuss ongoing challenges and clinical translation potential of CM-NMs to provide guidance for next-generation CM-NMs.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100404"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154423","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}
Qinghua Lan , Miao Wang , Yanyan Zhu , Xiayan Zhang , Ruolei Ye , Zhengbo Wu , HaiCi Lan , Songmei Luo , Yanyan Xu
{"title":"Bioinspired pH-sensitive liposomes for quercetin delivery to synergize with 5- FU in gastric cancer therapy","authors":"Qinghua Lan , Miao Wang , Yanyan Zhu , Xiayan Zhang , Ruolei Ye , Zhengbo Wu , HaiCi Lan , Songmei Luo , Yanyan Xu","doi":"10.1016/j.ijpx.2025.100437","DOIUrl":"10.1016/j.ijpx.2025.100437","url":null,"abstract":"<div><div>Gastric cancer is a major cause of cancer-related mortality on a global scale. Although 5-fluorouracil (5-FU) is a cornerstone chemotherapeutic for digestive tract malignancies, its efficacy is limited by dose-dependent toxicity and acquired resistance. Quercetin (QUC), a natural flavonoid, can sensitize tumor cells to 5-FU by modulating cell cycle-regulatory proteins. However, its limited water solubility and low bioavailability present significant limitations on its potential therapeutic application. In this study, we developed bioinspired pH-sensitive liposomes (NK-Lip@Q) functionalized for active targeting and acid-triggered drug release to enhance QUC delivery and synergistic anticancer activity with 5-FU. NK-Lip@Q exhibited a mean particle size of 206.36 ± 1.81 nm, an encapsulation efficiency of 60.69 ± 1.32 %, and a pH-dependent release profile with 72.75 ± 0.69 % cumulative release at pH 5.4. Cellular studies demonstrated efficient uptake by N87 cells, marked apoptosis induction (apoptosis ratio: 69.60 ± 8.71 %), and enhanced cytotoxicity in combination with 5-FU (Chou-Talalay combination index, CI = 0.68). In vivo, NK-Lip@Q could precisely accumulate in the target area, when co-administered with 5-FU, achieved significant tumor inhibition (tumor inhibition rate: 92.26 %) without obvious systemic toxicity. QUC complemented the anticancer action of 5-FU by regulating cell cycle-related genes, promoting apoptosis, and suppressing proliferation. In conclusion, this study demonstrates that NK-Lip@Q as a promising nanocarrier system that enhances the therapeutic performance of 5-FU by improving its synergistic antitumor efficacy in gastric cancer.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100437"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462891","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}
L.A. Lefol , A. Sodano , P. Bawuah , J.A. Zeitler , J. Verin , F. Danede , J.F. Willart , J. Siepmann , F. Siepmann
{"title":"Release mechanisms of PLGA microparticles prepared using a microfluidics device or a beaker","authors":"L.A. Lefol , A. Sodano , P. Bawuah , J.A. Zeitler , J. Verin , F. Danede , J.F. Willart , J. Siepmann , F. Siepmann","doi":"10.1016/j.ijpx.2025.100366","DOIUrl":"10.1016/j.ijpx.2025.100366","url":null,"abstract":"<div><div>The aim of this study was to better understand the release mechanisms of poly(lactic-<em>co</em>-glycolic acid) (PLGA) microparticles prepared via emulsification - solvent extraction/evaporation using a “classical beaker” vs. a “microfluidics device”. Ibuprofen-loaded microparticles were studied by optical microscopy, SEM, X-ray powder diffraction, X-ray μCT and drug release measurements from <em>single</em> microparticles in well agitated phosphate buffer pH 7.4 or agarose gel (mimicking living tissue). The use of a microfluidics device facilitated the preparation of microparticles with a less broad size distribution. However, in addition to the microparticle size, the inner system structure was found to be also of utmost importance for the resulting drug release kinetics in this case. Interestingly, even microparticles with <em>similar size, composition and inner & outer structure</em> exhibited a <em>broad spectrum of individual drug release patterns</em>. This was true, irrespective of the type of preparation method and experimental release set-up, and could be explained as follows: The investigated microparticles were characterized by a continuous inner pore network and an initially smooth & non-porous surface. Drug release set on as soon as: (i) the pore network got direct access to the release medium (e.g., due to a “weak point” in the PLGA surface layer), or (ii) substantial system swelling started (after a lag-time of several days). Importantly, <em>each</em> microparticle had its own, specific structure, which determined “<em>its way</em>” to release the drug. Furthermore, the experimental conditions were found to be of key importance: The presence of a surrounding agarose gel protected the microparticles from damage caused by convective fluid flow, and hindered microparticle swelling, thus, slowing down drug release.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100366"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749162","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}
Teng Xiao , Fanghong Wang , Ye Li , Gaoyang Lin , Xiaochen Wu
{"title":"Phloretin-loaded selenium nanoparticles for alleviating cisplatin-induced acute kidney injury via inhibition of the cGAS/STING pathway","authors":"Teng Xiao , Fanghong Wang , Ye Li , Gaoyang Lin , Xiaochen Wu","doi":"10.1016/j.ijpx.2025.100427","DOIUrl":"10.1016/j.ijpx.2025.100427","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a severe clinical condition with high morbidity and mortality, often triggered by nephrotoxic drugs like cisplatin. The cGAS/STING pathway, activated by DNA damage, plays a critical role in cisplatin-induced AKI. This study explores the potential of phloretin-loaded selenium nanoparticles (Phl/HS15-Se) as a therapeutic strategy to mitigate cisplatin-induced nephrotoxicity. Phloretin, a natural flavonoid with antioxidant properties, was encapsulated in polyethylene glycol (15)-hydroxy stearate (HS15) micelles and combined with selenium nanoparticles to enhance its renal protective effects. The <em>in vitro</em> and <em>in vivo</em> experiments demonstrated that Phl/HS15-Se significantly reduced oxidative stress, DNA damage, and inflammation by inhibiting the cGAS/STING pathway. In a cisplatin-induced AKI mouse model, Phl/HS15-Se alleviated renal pathological injury, improved renal function, and reduced the expression of inflammatory markers. This study provides a promising nanomedicine approach for the treatment of cisplatin-induced AKI by targeting the cGAS/STING pathway.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100427"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415830","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}