International Journal of Pharmaceutics: X最新文献

{"title":"PEGylated gold nanoparticles regulate metabolic flux in erythrocytes by inducing hemoglobin deoxygenation","authors":"Zeng He ,&nbsp;Wanjing Li ,&nbsp;Qin Zhao ,&nbsp;Doudou Hao ,&nbsp;Rui Zhong ,&nbsp;Hong Wang ,&nbsp;Xiaojie Zhang ,&nbsp;Libo Du ,&nbsp;Xiaodong Wu ,&nbsp;Jiaxin Liu","doi":"10.1016/j.ijpx.2026.100495","DOIUrl":"10.1016/j.ijpx.2026.100495","url":null,"abstract":"<div><div>Nanomedicines based on polyethylene glycol-functionalized gold nanoparticles (Au@PEG NPs) are usually administered by intravenous injection to improve bioavailability. It is widely accepted that surface modification with PEG can prevent direct interactions between AuNPs and proteins. Therefore, the interaction of Au@PEG NPs with plasma proteins and blood cells has not received enough attention. Our previous study demonstrated that Au@PEG NPs affect the oxygen-carrying capacity and deformability of erythrocytes through oxidative stress; however, the molecular mechanism of oxidative damage induced by Au@PEG NPs remains unclear. Due to the absence of cell organelles such as the nucleus and mitochondria in mature erythrocytes, we hypothesise that Au@PEG NPs primarily generate oxidative stress by interfere with metabolic flux in erythrocytes. We have employed dynamic light scattering (DLS), isothermal titration calorimetry (ITC) and surface plasmon resonance imaging (SPRi) to investigate the interaction between proteins and 30 nm Au@PEG NPs. ITC and SPRi data revealed that hemoglobin exhibits a higher affinity for 30 nm Au@PEG NPs compared to albumin (Ka: 1.46 × 10⁻⁴ <em>vs</em> 1.08 × 10⁻⁴ M⁻¹). Circular dichroism (CD) spectrum demonstrated a significant conformational shift in hemoglobin following incubation with 30 nm Au@PEG NPs, characterized by an increase in α-helix [(65.9 ± 0.6) % to (68.2 ± 0.6) %] and a decrease in β-sheet [(4.8 ± 0.3) % to (1.7 ± 0.2) %], which is consistent with its transition toward a deoxygenated state. By combining ICP-MS and four specific endocytosis inhibitors, we investigated the endocytic mechanism of Au@PEG NPs entering erythrocytes. The data revealed that the uptake efficiency of 30 nm Au@PEG NPs by erythrocytes was 68.2 ± 0.6 ng/10⁹ RBCs, with approximately 75% of the Au@PEG NPs were uptaked by erythrocytes through a mechanism involving caveolin- and clathrin-mediated endocytosis. Metabolomics and NADP⁺/NADPH analysis revealed that Au@PEG NPs induce hemoglobin deoxygenation, which in turn inhibits the pentose phosphate pathway and disrupts redox homeostasis, as reflected by the decrease of intracellular NADPH from 3.53 ± 0.50 nmol/10¹² RBCs to 2.67 ± 0.46 nmol/10¹² RBCs. However, tail vein injection of Au@PEG NPs did not impair the liver oxygen supply since mice can compensate for the hemoglobin deoxygenation effect of Au@PEG NPs by decreasing systolic blood pressure and increasing tissue perfusion. Our findings showed that Au@PEG NPs interfere with metabolic flux and generate oxidative stress in erythrocytes by changing the oxygenation state of hemoglobin, and these results suggest that future studies should pay more attention to hemocompatibility evaluations of nanomedicines before their clinical application.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100495"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074140","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":"Encapsulating GSH/NQO1-responsive SN38 prodrug micelles with Timosaponin AIII-based multifunctional liposomes for tumor-targeted chemotherapy","authors":"Xu Luo ,&nbsp;Ziqiong Yang ,&nbsp;Jianqiu Chen ,&nbsp;Mengqi Shen ,&nbsp;Kun Wang ,&nbsp;Qian Du","doi":"10.1016/j.ijpx.2026.100497","DOIUrl":"10.1016/j.ijpx.2026.100497","url":null,"abstract":"<div><div>Colorectal cancer chemotherapy faces challenges with low intratumoral drug accumulation and off-target toxicity. Micellar liposome complex carriers are a promising anti-cancer platform due to their high encapsulation efficiency, responsive release, and multi-targeting capabilities. This study explores a novel tumor-targeted chemotherapy approach by encapsulating GSH/NQO1-responsive SN38 prodrug micelles into cholesterol-replacement multifunctional liposomes. Timosaponin AIII (TAIII), a steroid saponin with anticancer activity, substitutes cholesterol to stabilize liposomes, benefiting from its steroidal aglycone structure. Additionally, TAIII mimics PEGylation via its glucose moiety, enhancing tumor targeting via the overexpression of glucose transporter 1 (GLUT1) on cancer cells. Molecular docking studies with AutoDock revealed that GLUT1 residues stabilize TAIII in the binding pocket through hydrogen bonding, hydrophobic, and polar interactions, promoting its transmembrane transport. A specific amphiphilic SN38 prodrug, PEG-SS-SN38-QPA (PSSQ), was synthesized and self-assembled into micelles via a solvent injection-dialysis method for GSH/NQO1-responsive controlled drug release in the tumor microenvironment. PSSQ micelles were integrated into the hydrophilic cavity of TAIII-based liposomes (TLP, prepared by the thin-film hydration method) through passive encapsulation to form PSSQ@TLP. In vitro release study exhibiting GSH/NQO1-triggered release under simulated tumor microenvironment. In vitro cytotoxicity evaluation was performed using the MTT assay on HCT116, LOVO, CT26.WT cell lines. Following in vivo evaluations of biodistribution, anti-tumor efficacy, and biosafety in CT26.WT xenograft tumor-bearing mice, PSSQ@TLP demonstrated enhanced intratumoral accumulation, robust tumor suppression, and minimized systemic toxicity, underscoring its promise as a targeted therapeutic strategy for colorectal cancer.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100497"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074141","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":"Ensuring vaccine cold chain integrity: A rapid and low-cost test for identifying heat-exposed sucrose-containing vaccines","authors":"Benediktus Yohan Arman ,&nbsp;Andrea Magri ,&nbsp;Matteo N. Barbaglia ,&nbsp;Lawrence Petherbridge ,&nbsp;Jennifer Brook ,&nbsp;Tehmina Bharucha ,&nbsp;Isabelle Legge ,&nbsp;John Walsby-Tickle ,&nbsp;Michael Deats ,&nbsp;Sneha Banerjee ,&nbsp;Sara Mosca ,&nbsp;Rajender Jena ,&nbsp;Dnyanesh S. Ranade ,&nbsp;Shrikrishna R. Chunekar ,&nbsp;Kundan D. Patil ,&nbsp;Sunil Gairola ,&nbsp;Hamid A. Merchant ,&nbsp;Robert Stokes ,&nbsp;Rutendo Kuwana ,&nbsp;Alexandrine Maes ,&nbsp;Bevin Gangadharan","doi":"10.1016/j.ijpx.2025.100467","DOIUrl":"10.1016/j.ijpx.2025.100467","url":null,"abstract":"<div><div>Maintaining cold-chain integrity is vital for vaccines to ensure that they remain within the recommended temperature limits during routine storage and transportation. This ensures vaccine stability, efficacy, and avoids degradation. Here, we propose rapid and low-cost tests based on simple glucose assays to detect heat-exposed degraded sucrose-containing vaccines through sucrose's inherent gradual conversion to glucose when exposed to elevated temperatures. Bioluminescent and colorimetric assays and a clinical biochemical analyser for urine samples could successfully determine effects of heat exposure on vaccines by detecting a significant increase in glucose levels. We show that this increase in glucose also correlates with the loss of vaccine potency. When vaccines were incubated at 37 and 45 °C, the bioluminescent assay was able to detect an increase in glucose levels from 12 h of heat exposure. The biochemical analyser could successfully detect increased glucose levels in a COVID-19 vaccine which had been exposed to 37 and 45 °C. Most importantly, the colorimetric assay has the advantage of producing a colour change visually upon simply mixing the vaccine with a reagent without the need for a plate reader or any other sophisticated devices. To our knowledge, this is the first simple, rapid and device-free test of its kind to detect heat-exposed substandard vaccines, making it a potential test for deploying at key points in the supply chain in warm and hot countries to check the integrity of vaccine cold-chain. Although this test does not replace the more definitive lot release assays such as potency assays, it could initially be used as a rapid and low-cost test to identify substandard sucrose-containing vaccines within supply chains, in support of WHO's Prevent, Detect, and Respond strategy.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100467"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765679","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":"Photothermally-activated nano-delivery system for on-demand treatment of diabetic wound infections","authors":"Rong Huang ,&nbsp;Wenjia Yang ,&nbsp;Tao Wang ,&nbsp;Xianbin Cao ,&nbsp;Shiyu Sun ,&nbsp;Jiaxin Jiang ,&nbsp;Hongsheng Liu ,&nbsp;Jianzhong Peng","doi":"10.1016/j.ijpx.2025.100464","DOIUrl":"10.1016/j.ijpx.2025.100464","url":null,"abstract":"<div><div>Bacterial-infected diabetic wounds, characterized by a persistent hyperglycemic environment, susceptibility to secondary bacterial infections, and chronic inflammatory responses, often exhibit impaired healing processes, posing a significant challenge in clinical management. To address this issue, this study designed and constructed a near-infrared (NIR) light-activated intelligent hydrogel drug delivery system—LSZBP@CMO. This system integrates highly efficient photothermal conversion components with a pH-responsive CMO hydrogel based on Schiff base reactions, achieving a dual-stimuli responsive drug release mechanism governed by exogenous NIR light and endogenous microenvironmental acidity. Under NIR irradiation, localized mild hyperthermia is generated, leading to the disruption of thermosensitive structures within the system and exposure of nanoparticles. This process, synergizing with the mildly acidic environment, further triggers rapid drug release, significantly enhancing antibacterial efficacy. Both in vitro and in vivo experimental results demonstrated that LSZBP@CMO not only efficiently eliminates bacteria but also effectively alleviates oxidative stress, modulates the inflammatory microenvironment, and markedly promotes angiogenesis, collagen deposition, and epithelial regeneration. In a diabetic rat model with infected wounds, the treatment group exhibited outstanding repair performance, achieving a wound healing ratio of 97.39 ± 1.60 % by day 7. This study provides an actively controllable strategy with promising clinical application prospects for on-demand therapy of refractory bacterial-infected diabetic wounds.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100464"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and evaluation of clotrimazole microemulsions for topical application: Effects of HLB value of surfactant mixture and cosurfactant type on formulation design","authors":"Chih-Wun Fang ,&nbsp;Yu-Wen Lin ,&nbsp;I-Hui Chiu ,&nbsp;Pao-Chu Wu","doi":"10.1016/j.ijpx.2025.100469","DOIUrl":"10.1016/j.ijpx.2025.100469","url":null,"abstract":"<div><div>Clotrimazole is a synthetic imidazole with broad-spectrum antimycotic effect that has been widely used for the topical treatment for athlete's foot (tinea pedis), oropharyngeal and vulvovaginal candidiasis. The objective of the study was to develop a nano-delivery system containing to improve the penetration capacity of Clotrimazole. Microemulsions were formulated and the chemophysical properties, permeability through rat skin and irritancy examined by HET-CAM test of drug-loaded formulations and stability were evaluated. The average droplet size and viscosity of all clotrimazole-loaded microemulsion formulations were respectively between 126.7–228.13 nm with PDI value less than 0.31 and 24.53–155.16 mPa·s. The penetration capacity of clotrimazole was markedly improved by using microemulsion formulations as delivery carriers: the 24-h cumulative permeated amount from the optimized microemulsion was approximately three-fold higher than that from the clotrimazole solution (drug dissolved in 30 % ethanol) and about 6.5-fold higher than that from the commercial product. The HET-CAM test showed the irritancy on skin of designed clotrimazole-loaded formulation was acceptable compared to the positive control of 0.8 % paraformaldehyde aqueous solution. The stability studies showed that the physicochemical characteristics and residual drug percentage (about 95.3 %) of F2 clotrimazole-loaded formulation were fairly stable after thermodynamic and storage tests, indicating designed microemulsions as a delivery carrier could be considered as a potential strategy for clotrimazole topical dosage form deployment.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100469"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145799440","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":"Gemini surfactant-stabilized cubosomes for enhanced topical delivery of 5-fluorouracil in cutaneous squamous cell carcinoma","authors":"Ruchira Raychaudhuri ,&nbsp;Ajinkya Nitin Nikam ,&nbsp;Naitik Jain ,&nbsp;Abhisheik Eedara ,&nbsp;Neha Kandpal ,&nbsp;Rajdeep Ray ,&nbsp;Krishnadas Nandakumar ,&nbsp;Sai Balaji Andugulapati ,&nbsp;Srinivas Mutalik","doi":"10.1016/j.ijpx.2026.100504","DOIUrl":"10.1016/j.ijpx.2026.100504","url":null,"abstract":"<div><div>Cutaneous squamous cell carcinoma (cSCC) is a prevalent non-melanoma skin cancer. Topical chemotherapy offers a non-invasive alternative to surgical treatments, yet the therapeutic efficacy of conventional agents like 5-fluorouracil is hindered by poor skin permeability and systemic side effects. In this study, we developed a gemini-surfactant-stabilized cubosomal gel (OF12-GEL) for enhanced topical delivery of 5-fluorouracil. The optimized cubosomes (OF12) exhibited a particle size of 134.4 nm, PDI 0.23, zeta potential +76.1 mV, and 51.3% entrapment efficiency. OF12-GEL achieved 41% release at 24 h and increased skin deposition to 323.7 μg/cm², nearly 3-fold higher than free 5-FU (114.1 μg/cm²). In A431 cells, OF12 showed a lower IC₅₀ (0.77 μg/mL) than free 5-FU (1.15 μg/mL) and enhanced cellular uptake. <em>In vivo</em>, OF12-GEL significantly suppressed tumor growth in both DMBA-induced SCC rats and A431 xenograft mice, reducing tumor volume by and improving survival to 60%, and markedly downregulating BCL-2, Ki67, TNF-α, and ABCB1. OF12-GEL was non-irritant (PII = 0.33). These findings demonstrate a potent, safe, and targeted nanocarrier-based topical therapy for cSCC.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100504"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188933","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":"Recent advances in lipid nanoparticles for cancer vaccine delivery: Challenges and future perspectives","authors":"Nurhasni Hasan ,&nbsp;Maryam Aftab ,&nbsp;Sania Ikram ,&nbsp;Apon Zaenal Mustofa ,&nbsp;Sriwidodo Sriwidodo ,&nbsp;Huda Shalahudin Darusman ,&nbsp;Muhammad Nur Amir ,&nbsp;Theofilus A. Tockary ,&nbsp;Satoshi Uchida","doi":"10.1016/j.ijpx.2026.100484","DOIUrl":"10.1016/j.ijpx.2026.100484","url":null,"abstract":"<div><div>Cancer remains a major global health burden, with 19.3 million new cases and 10.3 million deaths reported in 2020. Conventional modalities such as surgery, radiotherapy, and chemotherapy often fail to prevent metastasis or recurrence. Cancer vaccination, which mobilizes durable, tumor-specific immunity, has gained traction, and LNPs have become pivotal to this approach. Originally optimized for siRNA, LNPs’ core–shell architecture protects nucleic acids, enhances cellular uptake, and enables efficient cytosolic delivery. Their clinical validation in infectious-disease messenger RNA (mRNA) vaccines has catalyzed rapid progress toward oncology applications. Preclinical and early-phase trials have indicated that mRNA-LNPs encoding tumor-associated antigens or patient-specific neoantigens can expand cytotoxic T cells and elicit preliminary antitumor activity. Key barriers remain. Manufacturing cost and batch consistency challenge scale-up. Physicochemical instability necessitates cold-chain logistics and complicates global deployment. Reactogenicity and anti-PEG antibodies increase safety and dosing concerns. Within tumors, immunosuppressive microenvironments, heterogeneous antigen expression, and suboptimal lymphoid targeting limit the efficacy of vaccines. This review describes the advances in LNP design (ionizable and biodegradable lipids, PEG alternatives, ligand-mediated targeting), formulation strategies (thermostable and lyophilized systems), and delivery routes (intranodal and intratumoral) to overcome these bottlenecks. It also highlights synergistic combinations with checkpoint blockade, radiotherapy, and innate agonists, and examines emerging pipelines leveraging AI-guided neoantigen discovery and quality control. By integrating material engineering, immunology, and translational evidence, we identified failure points and proposed a roadmap for next-generation LNP-based cancer vaccines. The goal is to accelerate progress from bench to clinic, while improving manufacturability, access, and durable patient benefits.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100484"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977960","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":"A pH-responsive dual-drug nanoplatform for stromal remodeling and enhanced chemotherapy via MMP3/TGF-β inhibition","authors":"Tao Tan ,&nbsp;Yihan Wang ,&nbsp;Ran Cheng ,&nbsp;Dongsheng Yang","doi":"10.1016/j.ijpx.2026.100489","DOIUrl":"10.1016/j.ijpx.2026.100489","url":null,"abstract":"<div><div>The dense, fibrotic extracellular matrix (ECM) generated by cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) presents a formidable physical barrier that severely limits the penetration and efficacy of chemotherapeutic agents. This study aimed to design and validate a pH-responsive, dual-drug nanosystem (RPAE-QM) capable of overcoming this stromal resistance by coordinated delivery of a stromal-modulating agent and a potent cytotoxic payload. The RPAE-QM nanosystem was constructed to co-encapsulate the stromal-modulating agent quercetin (Que) and the chemotherapeutic drug DM1. RPAE-QM exhibited significant pH-responsive drug release, leading to strong synergistic cytotoxicity and superior tumor destruction capability in 3D spheroid models. Mechanistic investigation provided a definitive explanation for this efficacy. Molecular docking and molecular dynamics simulations predicted that Que. has high affinity and exceptional kinetic stability when binding to MMP-3. Subsequent experiments confirmed the downstream consequences of this interaction: treatment with Que. caused dose-dependent inhibition of both MMP-3 and TGF-<em>β</em>₁ secretion from CAFs. Moreover, this was accompanied by a significant, concentration-dependent reduction in the phosphorylation of Smad2/3, a key downstream effector of the TGF-<em>β</em> signaling pathway. The RPAE-QM nanosystem provides an effective dual-action strategy, simultaneously addressing the stromal barrier while delivering a potent cytotoxic agent. Mechanistically, our findings indicate that Que. suppresses the pro-fibrotic MMP3/TGF-<em>β</em>/Smad signaling axis in our CAF model. This work therefore introduces a dual-action therapeutic concept, offering a mechanistically-defined approach to disrupt stromal barriers and improve drug efficacy at the pre-clinical proof-of-concept stage.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100489"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978487","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":"Tumor-responsive PEGylated mesoporous nanoparticles achieve enhanced chemotherapy and reduced toxicity in prostate cancer","authors":"Yangyang Song ,&nbsp;Xue Tan ,&nbsp;Kai Yu ,&nbsp;Yue Wang ,&nbsp;Jixue Wang","doi":"10.1016/j.ijpx.2026.100492","DOIUrl":"10.1016/j.ijpx.2026.100492","url":null,"abstract":"<div><div>Docetaxel (DTX) remains the first-line chemotherapeutic for advanced prostate cancer, however, its therapeutic efficacy remains limited by poor aqueous solubility, rapid systemic clearance, and severe dose-dependent toxicity. To overcome these constraints, we developed a PEGylated, disulfide-bridged hierarchical mesoporous silica nanocarrier (PEG–HMS) as a redox-sensitive delivery system for DTX (PEG–HMS–DTX). The nanostructure was fabricated by integrating disulfide-containing organosilanes into the silica framework and conjugating thiol-reactive PEG chains, thereby combining long circulation stability with tumor-selective release. Comprehensive physicochemical characterization confirmed uniform spherical morphology, an optimal hydrodynamic size (∼40–50 nm), attenuated surface charge following PEGylation, and high colloidal stability in physiological media, while disulfide linkages enabled responsive structural changes under reductive conditions. Drug release was minimal under physiological conditions (&lt;30% at 72 h) but markedly accelerated in the presence of glutathione (∼60% at 72 h). Compared with free DTX or non-PEGylated carriers, PEG-HMS-DTX exhibited stronger cellular uptake and enhanced cytotoxicity in RM-1 prostate cancer cells. In tumor-bearing mice, PEG-HMS-DTX achieved superior tumor accumulation (peak at ∼12 h), pronounced tumor growth inhibition (&gt;70%), minimal systemic toxicity, and elevated apoptosis characterized by increased cleaved caspase-3 and reduced PCNA/Bcl-2 expression. Collectively, this “stable-in-circulation, trigger-in-tumor” platform substantially improves intratumoral DTX delivery and apoptosis-driven antitumor efficacy, while maintaining systemic safety. These findings highlight PEG-HMS-DTX as a promising and generalizable strategy for prostate cancer chemotherapy, warranting further pharmacokinetic, immunogenicity, and GLP toxicology studies to support translational advancement.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100492"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074026","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":"Bioinspired and stimuli-responsive nanocomposites for targeted therapy in ovarian and endometrial tumors","authors":"Jihang Yao ,&nbsp;Lulu Liu ,&nbsp;Xiufei Teng ,&nbsp;Daming Chu ,&nbsp;Silu Ding ,&nbsp;Hui Li ,&nbsp;Hua Chang ,&nbsp;Jing Liu","doi":"10.1016/j.ijpx.2026.100493","DOIUrl":"10.1016/j.ijpx.2026.100493","url":null,"abstract":"<div><div>Ovarian and endometrial cancers pose significant therapeutic challenges due to late-stage diagnosis and resistance to traditional therapies. Recent progress in the development of multiscale, bioinspired, and stimuli-responsive nanocomposites presents promising avenues for targeted therapy. These nanocomposites, engineered across a range from micrometers to nanometers, utilize hierarchical structures to enhance drug delivery, reduce systemic toxicity, and improve therapeutic efficacy. Through the integration of nanoparticles, hydrogels, and polymeric nanocarriers, these materials can react to external stimuli such as pH, temperature, and magnetic fields, enabling precise and controlled release of therapeutic agents. This review examines the design principles of these sophisticated composites, concentrating on their capacity to replicate the tumor microenvironment and enhance targeting specificity in ovarian and endometrial cancers. Furthermore, it highlights current clinical obstacles, safety considerations, and the considerable potential of these materials in personalized gynecologic oncology, underscoring their efficacy at both macroscopic and nanoscopic levels.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100493"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164035","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}