Drug Delivery and Translational Research最新文献

{"title":"About the impact of medium chain fatty acids on the permeation enhancing effects of self-emulsifying drug delivery systems.","authors":"Annika Postina, Lana Molnar, Lena Werner, Andreas Bernkop-Schnürch","doi":"10.1007/s13346-026-02211-9","DOIUrl":"https://doi.org/10.1007/s13346-026-02211-9","url":null,"abstract":"<p><p>Self-emulsifying drug delivery systems (SEDDS) are widely utilized to enhance oral drug absorption; however, limited epithelial permeability remains a major barrier, particularly for hydrophilic drugs and macromolecules. Medium-chain fatty acids are promising permeation enhancers (PEs) due to their transient effects on epithelial barriers. In this study, caprylic acid (C8) and capric acid (C10) were systematically evaluated as PEs in SEDDS, with emphasis on the influence of ionization state and mode of presentation within the formulation. SEDDS were modified by incorporating C8 or C10 either as free acids (SEDDS-C8/C10@Acid), as dispersed sodium salts (SEDDS-C8/C10@Salt), or by external addition of sodium salts after emulsification (SEDDS-C8/C10@extSalt). SEDDS-C8/C10@Acid significantly enhanced cellular internalization in Caco-2, HEK, and HeLa cells, achieving up to a 2.5-fold increase compared with unmodified SEDDS. In contrast, salt-based systems showed approximately 1.5-fold lower cellular association than acid formulations, while exhibiting improved cellular tolerability. Permeation studies revealed pronounced epithelial permeation across Caco-2 monolayers for salt-modified SEDDS, with lucifer yellow permeation increasing up to 7-fold for both C8 and C10 systems. Consistently, mucus interaction studies demonstrated enhanced diffusion for salt-based formulations. Differences between C8- and C10-containing systems were minor, indicating that alkyl chain length was less influential than ionization state and formulation format. Overall, incorporation of the free acid PE primarily enhanced cellular association via increased membrane partitioning, whereas incorporation of the corresponding sodium salt more effectively promoted mucus diffusion and epithelial permeation. These findings identify ionization state and formulation-dependent presentation as key design parameters for permeation-enhancing lipid-based drug delivery systems.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"αB-crystallin elastin-like polypeptides for sustained ocular drug delivery.","authors":"Sara Aly Attia, Amanda M Tse, Ashley D Ramirez, Maryam Izadiar, Ying Liu, Hao Guo, Angela Albanese, Whitaker Cohn, Adrienne W MacKay, Paul M Seidler, Ram Kannan, Parameswaran G Sreekumar, John Andrew MacKay","doi":"10.1007/s13346-026-02210-w","DOIUrl":"10.1007/s13346-026-02210-w","url":null,"abstract":"<p><p>The unfolded protein response (UPR) has been mechanistically implicated in multiple ocular disorders, including age-related macular degeneration (AMD). Therapeutic intervention using an αB-crystallin-derived 'mini-cry' chaperone peptide has potential to restore proteostasis; however, its low molecular weight results in rapid ocular clearance. To prolong mini-cry's ocular effects, our team linked it with elastin-like polypeptides (ELPs). ELPs are thermoresponsive polymers that phase-separate into microscale coacervates. Provided ELPs do not interfere with biological activity, cry-ELPs could prolong intraocular retention and improve therapeutic effect. This study compares two cry-ELPs (cry-SI and cry-V96) designed to phase-separate following intravitreal administration. First, chaperone activity was assessed using tau protein aggregation assays, demonstrating that cry-V96 exhibited superior inhibition of tau seeding and fibril disaggregation. Second, modulation of the UPR was assessed in human retinal pigment epithelium cells using tunicamycin-induced stress. Both constructs suppressed PERK/ATF-4/CHOP signaling, with cry-V96 showing the most robust attenuation of ER stress. Third, cellular uptake and subcellular localization were analyzed by biochemical fractionation and Western blotting, revealing enhanced cellular uptake and association and stress-dependent nuclear localization of cry-ELPs, compared to controls. Fourth, the lead construct, cry-V96, was evaluated in vivo in rabbit eyes, where it formed a sustained intravitreal depot, exhibited prolonged retention, and showed no evidence of ocular toxicity by fluorescence imaging and optical coherence tomography (OCT). Finally, proteomic profiling using liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 59 proteins selectively enriched by cry-V96, implicating pathways involved in proteostasis, intracellular trafficking, and stress adaptation. Collectively, these findings establish cry-ELPs as multifunctional molecules that combine potent chaperone activity with sustained ocular delivery, providing a promising strategy for targeting UPR dysregulation in AMD and related degenerative diseases.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery of liothyronine by microneedle patch for the treatment of hypothyroidism.","authors":"Yasmine Gomaa, Tasnuba Hasin, Martin N Griffin, Thy C Nguyen, Richard K Noel, Laura O'Farrell, Elizabeth A McAninch, Ann Marie Kaiser, Levi B Wood, Mark R Prausnitz","doi":"10.1007/s13346-026-02214-6","DOIUrl":"https://doi.org/10.1007/s13346-026-02214-6","url":null,"abstract":"<p><p>Hypothyroidism is conventionally treated with thyroid hormone replacement via synthetic hormones, namely levothyroxine (LT₄), and in possible combination with liothyronine (LT₃), both administered orally. The supratherapeutic peaks and subtherapeutic troughs of LT₃ concentration after oral delivery may limit efficacy, as this pharmacokinetic profile does not mimic the relatively constant T₃ levels found in normal physiology. Microneedle patches (MNPs) provide a simple-to-use delivery method that can be formulated to achieve controlled drug release for extended periods of time. Here, we developed a MNP for LT₃ delivery into the skin as a first assessment of this approach. After examining a number of MNP formulations, we developed MNPs containing a range of different LT₃ doses in a poly(vinylpyrrolidone)-based formulation. The MNs effectively punctured the skin and achieved average LT₃ delivery efficiencies of 41-71%. LT₃ MNP administration to hypothyroid rats at three doses (10 µg, 100 µg, 1000 µg) produced elevated serum T₃ levels that persisted for 18-24 h, exhibiting a nonlinear dependence on LT₃ dose. This study established the feasibility of administering LT₃ by MNP that could be translated to enable improved therapy for patients with hypothyroidism.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Microneedle loaded with luteolin-colostrum-derived exosomes: a dropless approach for treatment of glaucoma.","authors":"Sarah A Elsherbiny, Amal H El-Kamel, Basant A Bakr, Lamia A Heikal","doi":"10.1007/s13346-026-02119-4","DOIUrl":"10.1007/s13346-026-02119-4","url":null,"abstract":"","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3574-3575"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery.","authors":"Raghu Raj Singh Thakur, Ismaiel A Tekko, Farhan Al-Shammari, Ahlam A Ali, Helen McCarthy, Ryan F Donnelly","doi":"10.1007/s13346-026-02073-1","DOIUrl":"10.1007/s13346-026-02073-1","url":null,"abstract":"","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3572-3573"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding DMG: current treatment options and prospective solutions using nanoparticles.","authors":"Ahmed Mohamed, Aleksey Lyzlov, Rachna Prasad, Rex A Moats, Mark D Krieger, Virendra R Desai, Ashley S Margol, Peter A Chiarelli, Meenakshi Upreti","doi":"10.1007/s13346-026-02164-z","DOIUrl":"10.1007/s13346-026-02164-z","url":null,"abstract":"<p><p>Diffuse Midline Gliomas (DMGs), which include the subset formerly known as Diffuse Intrinsic Pontine Glioma (DIPG), are associated with an extremely poor prognosis and a five-year survival rate below 2-3%. The devastating prognosis stems from an inherently invasive nature, a deep, anatomically restricted location, rapid cellular drug efflux mediated by transporters such as P-glycoprotein (ABCB1) and breast cancer resistance protein (BCRP/ABCG2), and an immunologically \"cold\" microenvironment. Coupled with limited Blood-Brain Barrier (BBB) permeability, these biological factors render conventional, therapeutic strategies minimally effective. Nanoparticles (NPs) offer novel opportunities to enhance drug delivery across the BBB by improving penetration-primarily through strategies such as receptor-mediated transcytosis or localized delivery approaches-thereby concentrating therapy at the tumor site, lowering systemic toxicity, and enabling integration of diagnostic imaging. Crucially, the distinct and targetable biology of this H3K27-altered disease, including alterations in ACVR1, PDGFRA, and CDK4/6 pathways, makes it a key focus for current nanomedicine research.This review evaluates how NP strategies have potential to provide adaptive solutions to overcome the hurdles in therapeutic development for DMG. It details the major NP platforms-including liposomal, polymeric, inorganic, and carbon-based nanomaterials- focusing on design principles like size, surface charge, and stealth coating to enhance targeted delivery for passive accumulation or receptor-mediated transport across the BBB. It explores theranostic applications that integrate real-time imaging (MRI, PET) with targeted, personalized therapy. Additionally, the role of high-Z metal NPs as radiosensitizers is discussed, highlighting their ability to increase DNA damage in tumor cells while protecting healthy tissue. Although early studies demonstrate strong in vitro efficacy, challenges in BBB penetration, intratumoral distribution and nanomaterial scaling still impede successful in vivo translation. Nanomedicine overcomes critical DMG barriers by enabling targeted, sustained, image-guided therapy. Achieving meaningful survival benefit for patients with DMG requires a multidisciplinary approach bridging neuro-oncology, advanced imaging, and nanomaterials development. Future research must prioritize four key areas: (1) optimizing NP properties for superior brainstem penetration, (2) leveraging DMG-specific markers for active delivery, (3) integrating theranostics for real-time monitoring, and (4) developing scalable, clinically compliant manufacturing.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3231-3257"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microneedles self-implanting Astragalus polysaccharides-hybridized composite hydrogel combined with minoxidil to enhance in situ anti-androgenetic alopecia.","authors":"Jiaqi Li, Meng Long, Fanjun Xu, Zulalan Abudureyimu, Jing Li, Teng Guo, Nianping Feng, Yongtai Zhang","doi":"10.1007/s13346-026-02053-5","DOIUrl":"10.1007/s13346-026-02053-5","url":null,"abstract":"<p><p>In the current study, polysaccharides (APS) extracted from the dried roots of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao were demonstrated to promote hair regeneration. However, with an average molecular weight of 20,000, they exhibit poor transdermal absorption. To enhance local efficacy, we synthesized chemically crosslinked hyaluronic acid (cHA) and prepared γ-cyclodextrin-modified potassium metal-organic frameworks (MOFs) loaded with minoxidil (MDX) (MDX@MOF).The aforementioned materials were mixed with APS to form soluble microneedles (MDX@MOF-APS/cHA-MNs). Their oblique spike structure facilitates local fixation after skin penetration. MOF-based drug loading increased MDX water solubility by ninefold, while cHA provided significant sustained-release effects.Furthermore, APS enhances the mechanical properties of hydrogel microneedles and optimizes drug delivery. Notably, APS promotes human hair follicular papilla cell proliferation in a dose-dependent manner and exhibits synergistic effects with MDX. Concurrently, MDX@MOF-APS/cHA-MNs significantly prolong drug retention time in the skin, effectively improving hair coverage and growth rate in androgenetic alopecia mice. In summary, APS emerges as a clinical candidate for treating androgenetic alopecia, while novel microneedles with unique composition and structure enrich topical delivery strategies.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3457-3476"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic studies and synergistic antitumor effects of cannabichromene and cannabidiol in drug-resistant breast cancers.","authors":"Mounika Aare, Sandeep Chary Padakanti, Arvind Bagde, Jassy Mary Lazarte, Satyanarayan Dev, Charles Lewis, Mandip Singh","doi":"10.1007/s13346-026-02057-1","DOIUrl":"10.1007/s13346-026-02057-1","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is highly aggressive with limited treatment options, and resistance to doxorubicin (DOX) further compromises outcomes. Cannabinoids such as cannabichromene (CBC) and cannabidiol (CBD) possess anticancer properties, but their combined effects in resistant TNBC remain unexplored. This study evaluated the antitumor efficacy of a CBC + CBD combination against DOX-resistant (DOX-RT) TNBC using in vitro, in vivo, and pharmacokinetic models. Cytotoxicity was assessed in DOX-RT MDA-MB-231 cells using 2D and 3D assays, with synergy confirmed by combination index (CI) analysis. Cell cycle and invasion assays were performed. Xenograft studies were conducted in BALB/c nude mice bearing DOX-RT tumors treated intraperitoneally with CBC (10 mg/kg), CBD (20 mg/kg), or CBC + CBD. Pharmacokinetics were evaluated in rats, complemented by GastroPlus™ simulations. CBC + CBD synergistically inhibited cell growth induced G0/G1 arrest, and reduced invasiveness by ~ 55% in a Transwell Matrigel invasion assay. In xenografts, combination therapy reduced tumor volume by two-folds compared to single treatments and fourfolds versus control. Western blotting revealed downregulation of MEK/ERK, PI3K/AKT/mTOR, Cyclin D1, CDK6, SOD2, and NF-κB. Pharmacokinetic studies showed co-administration increased Cmax and AUC without altering Tmax, supported by simulations predicting enhanced jejunal absorption. CBC + CBD co-therapy demonstrates synergistic efficacy against resistant TNBC by inhibiting oncogenic pathways and enhancing systemic exposure. This first study of its kind highlights CBC + CBD as a promising strategy to overcome DOX resistance in TNBC.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3534-3554"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From bench to bulk: exploring in-line homogenization for scale-up and continuous production of vesicular systems.","authors":"Kshitija M Phatak, Ankita N Yawalkar, Pradeep R Vavia","doi":"10.1007/s13346-026-02045-5","DOIUrl":"10.1007/s13346-026-02045-5","url":null,"abstract":"<p><p>Nanovesicular systems hold a significant promise for drug delivery, yet their clinical translation is hindered by challenges in scalability and reproducibility. This study introduces in-line homogenization as a continuous, organic solvent-free approach for scalable fabrication of bilayered unilamellar vesicles, NioTherms (Niosome-like) and ThermoSomes (Liposome-like), loaded with model hydrophobic (Posaconazole, PCZ) and hydrophilic (Dexamethasone Sodium Phosphate, DEX) drugs. Using a heat-mixing method as the baseline, formulations were scaled from 10 mL (1x) to 1 L (100x) via a rotor-stator-based in-line homogenizer. Process parameters including pump speed, homogenizer speed, cycle number, phase ratio and output rate were optimized. The resulting vesicles exhibited uniform particle size and entrapment efficiencies comparable to the lab-scale batches. The formation of vesicles, morphology, internal structure, and integrity of the formed particles was confirmed by TEM and SANS analysis. The system enabled rapid batch processing (< 5 min for 1 L) with substantial product yields up to 80%. The process demonstrated excellent reproducibility and eliminated the need for post-processing. This study establishes in-line homogenization as a robust, scalable platform for faster production of nanovesicular drug delivery systems, effectively bridging the gap between bench-scale development and continuous manufacturing.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3368-3380"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review of thermal ablation technologies for transdermal drug delivery: mechanisms, commercial products, and future smart systems.","authors":"Muhammad Murtaza, Salman Ali Khan, Hayat Khan, S K Safdar Hossain","doi":"10.1007/s13346-026-02081-1","DOIUrl":"10.1007/s13346-026-02081-1","url":null,"abstract":"<p><p>The skin is the body's largest organ and is considered as a protective barrier which acts as a highly impermeable region of the human body. But in recent times, it is recognized as a specialized organ that aids in the delivery of a wide range of drug molecules into the skin (intradermal drug delivery) and across the skin into systemic circulation (transdermal drug delivery, TDD). Transdermal administration remains an active research and development area as an alternative route for long- acting drug delivery. It avoids major drawbacks of conventional oral (gastrointestinal side effects, low drug bioavailability, and need for multiple dosing) or parenteral routes (invasiveness, pain, and psychological stress and bio-hazardous waste generated from needles), thereby increasing patient appeal and compliance. The bioavailability of a drug administered transdermally can be improved by several penetration enhancement techniques, which are broadly classified into chemical and physical techniques. Application of the mentioned techniques together with efforts of various scientific and innovative companies had made TDD a multibillion-dollar market and this has led to a growing market with a steady pipeline of new transdermal products receiving regulatory approval. Out of various techniques, thermal therapeutic methods including chemical heating, laser ablation, thermoporation, radiofrequency and photothermal therapy are the top listed emerging techniques. This review article mainly discussed about these thermal ablation techniques with their available commercial products along with advantages and disadvantages. This review also presented anatomy of the skin, penetration pathways across the skin, affecting factors and different generations and mechanisms of TDD. Briefly, this article discussed basics, mechanism, challenges, and future research and development directions of thermal-based TDDS.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3079-3115"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}