International Journal of Pharmaceutics: X最新文献

{"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":"2026-01-27","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":"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":"2026-01-26","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":"A prostate-specific membrane antigen targeted small molecule-drug conjugate for efficient prostate cancer therapy at a low dosage","authors":"Jingjing Zhang ,&nbsp;Fanchun Hu ,&nbsp;Caiting Deng ,&nbsp;Yuhan Ding ,&nbsp;Yuchen Yang ,&nbsp;Shupeng Han ,&nbsp;Jun Liu ,&nbsp;Feifei An ,&nbsp;Mingsong Shi","doi":"10.1016/j.ijpx.2026.100496","DOIUrl":"10.1016/j.ijpx.2026.100496","url":null,"abstract":"<div><div>Prostate-specific membrane antigen (PSMA), which is overexpressed in most prostate cancer cells, serves as an ideal target for precision therapy. The clinical utility of the potent chemotherapeutic agent SN38 is hindered by its poor water solubility and systemic toxicity. Herein, we present a novel, fully water-soluble small-molecule drug conjugate (SMDC), SN38-SS-3PEG₂₄-3PSMA (SPP), designed for enhanced prostate cancer targeting and tumor-selective drug release. SPP integrates three PSMA-targeting ligands, a glutathione (GSH)-responsive disulfide linker, and three monodisperse polyethylene glycol (PEG) chains, achieving exceptional water solubility (&gt;1 mM) and tumor-specific payload activation. In vivo fluorescence imaging revealed efficient tumor accumulation with minimal hepatic distribution, as evidenced by predominant renal clearance, thereby reducing hepatotoxicity risks. Remarkably, SPP demonstrated potent tumor growth inhibition at low doses (20 nmol) in PSMA-positive xenograft models, outperforming controls without PEG spacers or disulfide linkers. The GSH-triggered release of SN38 within the tumor cells ensured high cytotoxicity against cancer cells while maintaining stability in circulation, thereby minimizing off-target toxicity. Collectively, this study highlights SPP as a promising therapeutic candidate, combining enhanced water solubility, precise tumor targeting, and low-dose efficacy with an excellent safety profile, offering a transformative strategy for prostate cancer treatment.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100496"},"PeriodicalIF":6.4,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074027","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":"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":"2026-01-22","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":"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":"2026-01-13","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":"Chitosan-based nanozyme hydrogels: Advanced antioxidant and sustained-release systems for the prevention and treatment of skin photoaging","authors":"Qucheng Huang ,&nbsp;Xiaojun Zhang ,&nbsp;YuanYuan Zuo ,&nbsp;Leiyi Wang ,&nbsp;Huan Sun ,&nbsp;Hewei Xu ,&nbsp;Miao Yu ,&nbsp;Chang Liu","doi":"10.1016/j.ijpx.2026.100491","DOIUrl":"10.1016/j.ijpx.2026.100491","url":null,"abstract":"<div><div>Photoaging of the skin is a chronic damage process caused by prolonged exposure to ultraviolet radiation, characterized by increased oxidative stress, activation of inflammatory responses, and collagen degradation. However, photoaging of the skin presents challenges in prevention, limited efficacy of therapeutic agents, and difficulties in repairing the damage. In recent years, chitosan-based hydrogels, which exhibit excellent biocompatibility, biodegradability, film-forming properties, and the ability to deliver sustained-release medication, have progressively emerged as cutting-edge therapeutic agents for treating photoaging of the skin. Nanozymes are nanomaterials possessing enzymatic functions that effectively scavenge reactive oxygen species generated by ultraviolet irradiation, exhibiting excellent antioxidant properties. Loading nanozymes into chitosan-based hydrogels not only combines the biocompatibility of chitosan hydrogels with the antioxidant properties of nanozymes to enhance therapeutic efficacy but also enables stable loading and controlled release of drugs and active ingredients. This further improves treatment efficiency while fully leveraging the moisturizing and restorative properties of the hydrogel matrix. This paper systematically summarizes the construction methods, performance optimization, and mechanism of action of chitosan-based nanozyme hydrogels in preventing and treating skin photoaging. It focuses on analyzing research advances in their capacity to scavenge free radicals, alleviate inflammation, and promote skin barrier repair, while exploring their application prospects and challenges in skin repair and the cosmetics sector.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100491"},"PeriodicalIF":6.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977959","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":"Transferrin-modified multicomponent liposomes encapsulating paclitaxel-loaded β-elemene microemulsion enhance therapeutic efficacy in non-small-cell lung cancer","authors":"Yunyan Chen ,&nbsp;Ziwei Zhang ,&nbsp;Rui Xiong ,&nbsp;Yuqing Cao ,&nbsp;Qian Liu","doi":"10.1016/j.ijpx.2026.100488","DOIUrl":"10.1016/j.ijpx.2026.100488","url":null,"abstract":"<div><div>To achieve efficient accumulation and facilitate profound penetration of anti-tumor agents within neoplastic tissues stands as one of the most critical determinants influencing the efficacy of anticancer therapies. Herein, a multicomponent-based liposomes (Tf-PEM/L) by transferrin-modified encapsulating paclitaxel (PTX)-loaded <em>β</em>-elemene microemulsion (PEM) was fabricated, demonstrating significantly enhanced therapeutic efficacy against non-small cell lung cancer (NSCLC). Leveraging the synergistic mechanism of transferrin-mediated active targeting coupled with the enhanced permeability and retention (EPR) effect, Tf-PEM/L demonstrates a pronounced propensity for efficient and substantial accumulation at the tumor site. Following accumulation, the subsequently released PEM enables highly efficient deep penetration within tumor tissue, thereby achieving favorable anti-tumor therapeutic efficacy. Characterization of Tf-PEM/L revealed a mean particle size approximately (144.76 ± 9.34) nm, while the zeta potential exhibited a measurement of (−12.52 ± 0.28) mV. Notably, the transmission electron microscopy (TEM) images revealed the small-sized PEM were encapsulated within large-sized liposomes. In vitro cytotoxicity assays demonstrated that Tf-PEM/L elicited synergistic antitumor effects against A549 cells, underscoring its combinatorial therapeutic potential. In vivo studies, Tf-PEM/L demonstrated exceptional tumor-targeting capabilities as evidenced by quantitative biodistribution analyses. Moreover, Tf-PEM/L exhibited superior antitumor efficacy with tumor inhibition rate of (81.36 ± 3.87)% while markedly attenuating systemic toxicity, positioning it as a promising therapeutic strategy for NSCLC. Collectively, the Tf-PEM/L represents a promising targeted therapeutic strategy for NSCLC, with enhanced efficacy and safety profiles.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100488"},"PeriodicalIF":6.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978488","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":"Application of ultrasound and ultrasound-responsive materials in wounds: A systematic review","authors":"Jialei Luo ,&nbsp;Liwan Song ,&nbsp;Xinyi Yan ,&nbsp;Xiaolu Ma ,&nbsp;Jianqing Gao ,&nbsp;Ying Luo ,&nbsp;Gaoyi Yang","doi":"10.1016/j.ijpx.2026.100485","DOIUrl":"10.1016/j.ijpx.2026.100485","url":null,"abstract":"<div><div>Wound healing is a multifaceted biological process that is highly susceptible to disruption by numerous internal and external factors, resulting in delayed tissue repair. Recent advancements have highlighted the therapeutic potential of ultrasound, especially when integrated with emerging smart materials, which together offer promising strategies for enhancing wound care outcomes. Low- and high-intensity ultrasound (US) use mechanisms such as cavitation, acoustic streaming, and radiation forces to disrupt biofilms, improve drug permeability, and promote tissue regeneration. When combined with US-responsive materials, such as scaffolds, piezoelectric composites, microbubbles, microneedles, and flexible patches, these systems enable targeted functions, including controlled drug release, antimicrobial activity, and enhanced deep tissue penetration. These responsive materials effectively overcome the limitations of conventional wound dressings, which often suffer from poor drug bioavailability, susceptibility to infection, and a lack of personalized therapeutic capabilities. This review systematically explores 5 categories of advanced materials, with a focus on their synergistic interactions with ultrasound to enhance wound healing outcomes. By elucidating the interactions between material-US and their translational implications, this review offers new perspectives to advance the clinical development of precision-based, next-generation wound therapies.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100485"},"PeriodicalIF":6.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939598","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":"2026-01-08","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":"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":"2026-01-06","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}