Tamara Jordens, Anne-Jaël Elskamp, Imke H Bartelink
{"title":"Combining imaging strategies with physiologically-based pharmacokinetic modeling to improve precision dosing & drug delivery in brain tumors.","authors":"Tamara Jordens, Anne-Jaël Elskamp, Imke H Bartelink","doi":"10.1016/j.jconrel.2026.115451","DOIUrl":"10.1016/j.jconrel.2026.115451","url":null,"abstract":"<p><p>Small molecule targeted therapies frequently fail to control brain metastases and primary brain tumors even when systemic exposure reaches toxicity-limiting levels. Systemic exposure-response relationships are often absent, which is well documented for tyrosine kinase inhibitors. Target-site information is therefore needed, since the concentration reached in the tumor is determined not by plasma exposure, but by passive and active transport across the blood-brain barrier and by intratumoral heterogeneity. Physiologically-based pharmacokinetic (PBPK) modeling provides the mechanistic framework to describe this. Models built solely on in vitro-to-in vivo extrapolation of permeability and transport have repeatedly required correction factors derived from rodent data, and their evaluation in humans still depends on invasive sampling or microdialysis. Microdialysis performs poorly for lipophilic, highly protein-bound drugs. We argue that quantitative imaging can supply the missing in vivo input. In a hybrid strategy, in vitro-derived transport parameters serve as the starting point, while blood-brain barrier influx and efflux are recalibrated on positron emission tomography (PET) microdose measurements in patients. This could lead to improved prediction of brain concentrations at therapeutic doses and allows simulated target-site exposure to be weighed against in vitro potency for compound and dose selection. Beyond whole-brain averages, magnetic resonance imaging (MRI) can provide permeability and perfusion parameters longitudinally and in larger cohorts, whereas mass spectrometry imaging (MSI) techniques can map intratumoral heterogeneity in drug distribution in the tumor microenvironment and identify potential sanctuary sites. We map each modality onto the specific PBPK parameters it can inform, and argue that imaging-informed, spatially resolved PBPK is a realistic route toward model-informed precision dosing in neuro-oncology.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115451"},"PeriodicalIF":12.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Harnessing reactive oxygen species for advanced drug delivery and therapeutics","authors":"Jae Hyung Park,Andrew Wang,Hélder A. Santos","doi":"10.1016/j.jconrel.2026.115437","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115437","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"110 1","pages":"115437"},"PeriodicalIF":10.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ward Jacobs,Klarinda de Zwaan,Luco Rutten,Thierry van Wessel,Thomas J. Boltje,Laia Querol Cano,Christian Büll,Nico Sommerdijk,Lorenzo Albertazzi,Roland Brock
{"title":"The role of glycocalyx-protein corona interactions in the cell type-specific uptake of mRNA nanocarriers","authors":"Ward Jacobs,Klarinda de Zwaan,Luco Rutten,Thierry van Wessel,Thomas J. Boltje,Laia Querol Cano,Christian Büll,Nico Sommerdijk,Lorenzo Albertazzi,Roland Brock","doi":"10.1016/j.jconrel.2026.115440","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115440","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"24 1","pages":"115440"},"PeriodicalIF":10.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exosomes as next-generation drug carriers: Transforming cancer therapy.","authors":"Yaseera Arif, Disha Nagesh Moholkar, Raghuram Kandimalla, Farrukh Aqil, Ramesh C Gupta","doi":"10.1016/j.jconrel.2026.115265","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115265","url":null,"abstract":"<p><p>Cancer remains a major global health challenge, with its growing incidence highlighting the critical need for effective and accessible treatments. Current therapeutic approaches, including surgery, chemotherapy, radiation therapy, hormone therapy, and immuno-therapy, are often limited by toxicity, poor targeting, and suboptimal efficacy. These challenges have driven the development of nanotechnology-based strategies aimed at improving tumor selectivity and therapeutic outcomes. Among the most promising are extracellular vesicles, particularly exosomes (30-150 nm), which have garnered significant attention as natural nanocarriers due to their inherent role in intercellular communication and their capacity to encapsulate proteins, nucleic acids, and lipids. Exosomes can be obtained from a wide range of sources, including biological fluids, cell cultures, and unconventional origins such as plants and microorganisms. Of particular interest are milk- and colostrum-derived exosomes, particularly those of bovine origin, have emerged as a promising delivery platform owing to their scalability, biocompatibility, cost-effectiveness and suitability for oral administration. These vesicles possess immunomodulatory properties, demonstrate stability under gastrointestinal conditions, and are readily internalized by intestinal epithelial cells. Furthermore, surface engineering with targeting ligands such as folic acid can enhance tumor specific delivery by exploiting receptor overexpression while minimizing systemic toxicity. This review critically examines exosome sources, isolation and characterization methodologies, cargo-loading strategies, biodistribution, pharmacokinetics, and engineering approaches together with their applications in delivering small-molecule drugs and nucleic acid-based therapeutics to overcome multidrug resistance in cancer. In addition, current challenges related to exosome heterogeneity, manufacturing, quality control, clinical translation, and regulatory considerations are discussed, together with future perspectives for the development of exosome-based therapeutics.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115265"},"PeriodicalIF":12.4,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Controlled-release hydrogel loaded with engineered extracellular vesicles for treatment of chronic endometritis.","authors":"Haixia Li, Ruixue Hu, Yue Zhang, Junli Zhang","doi":"10.1016/j.jconrel.2026.115267","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115267","url":null,"abstract":"<p><p>Chronic endometritis (CE) is an important factor contributing to infertility and adverse pregnancy outcomes. Current clinical management mainly relies on antibiotics such as ceftizoxime (CTX), whose efficacy is limited by poor oral bioavailability and short half-life. To address these limitations, this study developed an intelligent, responsive hydrogel incorporating Leonurus japonicus Houtt derived extracellular vesicles (EVs) loaded with CTX. The hydrogel forms sustained-release drug reservoir in situ within the uterine cavity, enabling controlled release in response to the local inflammatory microenvironment. EVs can effectively regulate the inflammatory microenvironment by inhibiting activation of NF-κB pathway and NLRP3 inflammasome, downregulating the pro-inflammatory factor TGF-α, and upregulating the anti-inflammatory factors IL-10 and TGF-β1, thereby significantly promoting endometrial repair and reducing fibrotic areas. Meanwhile, CTX provides targeted antibacterial activity to eliminate pathogens and control infection. Through exerting antibacterial, anti-inflammatory, and tissue repairing, the developed intelligent, responsive hydrogel system offers a promising strategy for treatment of CE.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115267"},"PeriodicalIF":12.4,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mary D. Kelly, Timothy Q. Vu, Atiriya U. Iyer, Yiming Luo, Aiden P. Linderman, Lariana Cline, Crystal Sanchez, Neha P. Kamat
{"title":"DNA-directed assembly of multivalent lipid nanoparticles for targeted T cell gene delivery","authors":"Mary D. Kelly, Timothy Q. Vu, Atiriya U. Iyer, Yiming Luo, Aiden P. Linderman, Lariana Cline, Crystal Sanchez, Neha P. Kamat","doi":"10.1016/j.jconrel.2026.115018","DOIUrl":"10.1016/j.jconrel.2026.115018","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"396 ","pages":"Article 115018"},"PeriodicalIF":12.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148225638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keiichiro Kushiro, Morgan McSweeney, Scott Hammers, David Quan, Yong Zhu, Haley B. Flowers, Lauren Dawson, Jinping Yang, Gengi Kleto, Cynthia Cabrales, Alison Schaefer, Katherine Gibb, Richard Cone, Thomas Moench, Kathleen L. Vincent, Samuel K. Lai
{"title":"Corrigendum to ‘A versatile capsule-intravaginal ring platform enables rapid and sustained release of monoclonal antibodies for non-hormonal contraception’ [Journal of Controlled Release 394 (2026) 114886]","authors":"Keiichiro Kushiro, Morgan McSweeney, Scott Hammers, David Quan, Yong Zhu, Haley B. Flowers, Lauren Dawson, Jinping Yang, Gengi Kleto, Cynthia Cabrales, Alison Schaefer, Katherine Gibb, Richard Cone, Thomas Moench, Kathleen L. Vincent, Samuel K. Lai","doi":"10.1016/j.jconrel.2026.114978","DOIUrl":"10.1016/j.jconrel.2026.114978","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"396 ","pages":"Article 114978"},"PeriodicalIF":12.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}