Shafi Ullah , Grace Victoria Poo , Ge Yan , Shen Xin , Qiao Chunrui , Amna Aziz khan , Qi Zhenhui
{"title":"Nanocarrier-engineered therapeutics for Glioblastoma: Challenges and strategies for overcoming the blood-brain barrier","authors":"Shafi Ullah , Grace Victoria Poo , Ge Yan , Shen Xin , Qiao Chunrui , Amna Aziz khan , Qi Zhenhui","doi":"10.1016/j.jddst.2026.107998","DOIUrl":"10.1016/j.jddst.2026.107998","url":null,"abstract":"<div><div>Glioblastoma (GBM) remains one of the most lethal primary brain tumors, with patient prognosis severely hampered by the blood-brain barrier (BBB) and the tumor's aggressive and heterogeneous nature. Although nanocarrier-mediated drug delivery to cross the BBB has been extensively studied, existing reviews largely focus on conventional platforms such as liposomes and polymeric nanoparticles. The novelty of this review lies in its critical comparative analysis of emerging nanocarriers—carbon nanodots, hybrid lipid–polymer systems, peptide-guided nanocarriers, and lipoprotein-based nanodiscs—integrated with recent in vivo findings and translational considerations. This review is offering a comparative perspective on nanocarrier design, mechanisms of BBB penetration, and therapeutic efficacy in GBM. Furthermore, we evaluate the translational potential of these systems, discussing key challenges such as toxicity, scalability and immunogenicity, while outlining future directions involving AI-driven design and personalized nanomedicine. By synthesizing and critically assessing the current landscape, this review aims to guide future research toward clinically viable nanocarrier solutions for GBM.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 107998"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980829","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":"CD44-targeted and pH-degradable hollow mesoporous silica nanocarriers for cancer therapy","authors":"Yi-Ching Tsai , Natesan Thirumalaivasan , Shu-Pao Wu","doi":"10.1016/j.jddst.2026.108045","DOIUrl":"10.1016/j.jddst.2026.108045","url":null,"abstract":"<div><div>Targeted drug delivery systems are crucial for cancer treatment, as they boost therapeutic effectiveness while minimizing systemic toxicity. In this study, we developed pH-degradable hollow mesoporous silica nanoparticles (HMON) functionalized with hyaluronic acid (HA) for CD44-targeted drug delivery. Aryl imine organosilane was utilized to confer pH-responsiveness to the HMON, enabling controlled drug release in the mildly acidic tumor microenvironment. In vitro studies have shown that <strong>DOX@HMON-HA</strong> significantly enhances DOX uptake in CD44-overexpressing tumor cells, such as HeLa and HCT-116, leading to substantial cytotoxic effects. In contrast, CD44-low expressing cells like MCF-7 exhibit minimal DOX uptake and reduced cytotoxicity. In vivo studies further validated the therapeutic efficacy of <strong>DOX@HMON-HA</strong>, showing effective tumor growth suppression without observable systemic toxicity. These findings underscore the potential of pH-degradable hyaluronan (HA)-modified silica nanoparticles as an effective strategy for targeted cancer therapy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108045"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035466","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":"Transforming waste into medicine: Wound healing potential of banana peel phytoconstituents","authors":"Raj Kamal , Abhishek Chauhan , Sonia Dhiman, Mohit Kumar, Thakur Gurjeet Singh, Ankit Awasthi","doi":"10.1016/j.jddst.2026.108052","DOIUrl":"10.1016/j.jddst.2026.108052","url":null,"abstract":"<div><div>Banana peel which is often discarded as waste, is a rich reservoir of bioactive compounds. It contains leucocyanidin, gallic acid, catechin, epicatechin, anthocyanins, tannins, biogenic amines, and carotenoids. These phytoconstituents play essential roles in tissue repair and wound healing through antioxidant, anti-inflammatory, and antimicrobial actions. Recent advances in extraction technologies, including ultrasound-assisted, microwave-assisted, enzymatic, and supercritical fluid extraction, have enabled efficient recovery of these compounds. Their identification and quantification are reliably achieved using High-Performance Liquid Chromatography, Liquid Chromatography–Mass Spectrometry, and spectrophotometry. Evidence from preclinical and clinical studies indicates that banana peel bioactives accelerate re-epithelialization, promote angiogenesis, enhance collagen deposition, and strengthen antioxidant defences. They also suppress oxidative stress, modulate inflammatory pathways, and reduce microbial burden, thereby supporting multiple stages of the wound healing cascade. Incorporation into nanoformulations, such as liposomes, polymeric micelles, and lipid nanoparticles, further improves stability, bioavailability, and therapeutic efficacy. Banana peel thus represents a safe, cost-effective, and environmentally sustainable source of wound healing agents. Its broad therapeutic potential and ability to address key determinants of chronic wound management underscore its promise for translation into advanced biomedical applications. Further research and clinical validation are required to develop scalable formulations capable of transforming waste-derived banana peel into effective, affordable, and eco-friendly wound care products.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108052"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397294","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}
Aiju Chen , Qiulu Wang , Xiangtai Wang , Lixia Yuan , Hui Yan , Lingfeng Gao , Min Liu
{"title":"Unveiling the structure-function relationship of natural deep eutectic solvents in enhancing the solubility, stability, and antioxidant activity of baicalein","authors":"Aiju Chen , Qiulu Wang , Xiangtai Wang , Lixia Yuan , Hui Yan , Lingfeng Gao , Min Liu","doi":"10.1016/j.jddst.2026.108083","DOIUrl":"10.1016/j.jddst.2026.108083","url":null,"abstract":"<div><div>Baicalein (Bai), a flavonoid with multiple pharmacological effects, suffers from poor solubility and low stability, limiting its therapeutic application. To overcome these limitations, biocompatible solvents with high solvation capacity present a simple and efficient strategy. In this work, three natural deep eutectic solvents (NADES) were prepared from choline chloride (ChCl) and structurally comparable organic acids: levulinic acid (LevA), lactic acid (LacA), and malic acid (MalA). These NADES exhibited good biocompatibility and were mixed with water to improve the solubility and stability of Bai. The solubility enhancement of Bai in these solvents followed the order: ChCl-LevA > ChCl-LacA > ChCl-MalA > water. Thermodynamic analysis revealed an entropy-driven dissolution process. To delve deeper into the dissolution mechanism, density measurements, FTIR spectroscopy, and molecular dynamics simulations were conducted to elucidate solvent-solvent and solute-solvent interactions. Additionally, the storage stability, photostability, and pH stability of Bai in NADES were also investigated. The results indicated that the differences in intermolecular interactions caused by different NADES exerted varying effects on the stability of Bai. The DPPH free radical scavenging assay was used to investigate the synergistic or antagonistic antioxidant effects between Bai and NADES, with the data analyzed by response surface methodology. These results are expected to provide a theoretical basis for the development of NADES-based solubilizers or drug carriers in pharmaceutical and food science.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108083"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397767","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":"Simultaneous evaluation of drug absorption and in vivo release behavior from coated mini tablets with Eudragit L 30 D-55 in rats using near-infrared imaging","authors":"Makoto Kataoka , Nanami Matsuura , Takato Masada , Keiko Minami , Haruki Higashino , Takuya Nagato , Shinji Yamashita","doi":"10.1016/j.jddst.2026.107996","DOIUrl":"10.1016/j.jddst.2026.107996","url":null,"abstract":"<div><div>We previously demonstrated the use of near-infrared (NIR) imaging to evaluate differences in disintegration for various capsule formulations after oral administration to rats. To further explore this techniques utility, <em>in vitro</em> and <em>in vivo</em> studies were conducted using mini tablets (2.5 mm in diameter and 2.17 mm in thickness) containing indocyanine green (ICG), acetaminophen (ACE), metoprolol tartrate (MET), and atenolol (ATE), prepared and coated with two different thicknesses of Eudragit® L 30 D-55. The <em>in vitro</em> results showed that the coated mini tablets exhibited acid resistance with slow leakage in acidic media and rapid release with a short lag time under neutral pH conditions as a function of coating thickness. Consistent with the <em>in vitro</em> dissolution profiles, oral drug absorption was also substantially affected by coating thickness. Although the <em>AUC</em> of ACE decreased only slightly, <em>C</em><sub>max</sub> decreased significantly, and <em>T</em><sub>max</sub> was prolonged with coating thickness increase. Similar trends in <em>C</em><sub>max</sub> and <em>T</em><sub>max</sub> were observed for MET and ATE; however, their <em>AUC</em>s decreased markedly with increasing coating thickness. ICG fluorescence intensity and area time profiles, which reflect the amount and extent of drug dissolved in the intestine, closely corresponded to the absorption profile of ACE quantified by deconvolution analysis, further suggesting distinct MET and ATE absorption characteristics. Collectively, these findings demonstrate that NIR imaging is a valuable tool for evaluating <em>in vivo</em> drug release from coated mini tablets.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 107996"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980186","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":"Inhibition of cholesterol absorption using flame-produced ZnO Nanoparticles: Potential applications in hyperlipidemia","authors":"Thanthakan Saithong , Kornwalai Tunkaew , Jakkapong Inchai , Pannita Holasut , Mameaseng Siriwalai , Chaikarn Liewhiran , Chutima S. Vaddhanaphuti","doi":"10.1016/j.jddst.2026.108054","DOIUrl":"10.1016/j.jddst.2026.108054","url":null,"abstract":"<div><div>Synthetic zinc oxide nanoparticles (ZnO-NPs) produced by flame spray pyrolysis (FZnO-NPs) have been extensively studied for applications due to a one-step synthesis process, high purity, large external surface area, high noble metal dispersion, and scalability. Although these benefits have been illustrated, their potential in biomedical fields remains underexplored. To pursue the potential implication of using FZnO-NPs in lowering lipid levels, therefore, this study aimed to investigate the potential lipid-lowering effect in the transluminal gastrointestinal environment compared with commercially available (CZnO-NPs). Comparable in pore sizes, surface area, purity, morphology, charge, and stability of each type were determined. Changes in the physicochemical properties of cholesterol micelles induced by each ZnO-NPs were investigated along with the absorption of green fluorescent-25-[N-[(7-nitro-2-1,3-benzoxadiazol-4-yl)methyl]amino]-27-norcholesterol in the human colorectal adenocarcinoma (Caco-2) cell line and further validated with tritium-cholesterol micelle transport in rats. The findings demonstrated that FZnO-NPs had a smaller size and larger surface area compared to CZnO-NPs. In addition, FZnO-NPs significantly inhibited cholesterol absorption in Caco-2 cells, similar to the effect of the positive drug, ezetimibe, with a lesser potency. Consistently, FZnO-NPs were mechanistically more effective in aggregating and expanding cholesterol micelle size than CZnO-NPs. Nonetheless, both nanoparticle types exhibited high affinity for binding to bile acids. Correspondingly, FZnO-NPs markedly decreased cholesterol absorption, reflected by reducing cholesterol levels in plasma, jejunal, and hepatic tissues, comparable to ezetimibe's effect in rats. Thus, this study suggested that FZnO-NPs had promising therapeutic potential for lowering cholesterol levels by inhibiting cholesterol absorption, which could be an option for preventing hyperlipidemia.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108054"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074423","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}
Tanyaradzwa Tiandra Dembetembe , Danielle Twilley , Jacqueline Maphutha , Marco Nuno De Canha , Velaphi Clement Thipe , Vusani Mandiwana , Michel Lonji Kalombo , Rirhandzu Rikhotso , Suprakas Sinha Ray , Namrita Lall , Quenton Kritzinger
{"title":"Gunnera perpensa L. - mediated gold nanoparticles with enhanced anti-gonococcal activity","authors":"Tanyaradzwa Tiandra Dembetembe , Danielle Twilley , Jacqueline Maphutha , Marco Nuno De Canha , Velaphi Clement Thipe , Vusani Mandiwana , Michel Lonji Kalombo , Rirhandzu Rikhotso , Suprakas Sinha Ray , Namrita Lall , Quenton Kritzinger","doi":"10.1016/j.jddst.2026.107977","DOIUrl":"10.1016/j.jddst.2026.107977","url":null,"abstract":"<div><div>Gonorrhoea is the second most prevalent sexually transmitted disease (STD) worldwide, with its treatment increasingly compromised by antibiotic resistance to available treatments. This has led to the investigation of bioactive plants as sources for novel drug development, with plant-based nanoparticles showing promise in treating STDs. This study aimed to evaluate the anti-gonococcal activity and cytotoxicity of the ethanolic root extract of <em>Gunnera perpensa</em> L. (GP) and to determine whether synthesis of gold nanoparticles (AuNPs) from GP showed enhanced biological activity. Characterization of the nanoparticles was performed using ultraviolet–visible spectrometry (UV–Vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), Zeta potential, Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Lastly, the anti-gonococcal activity and cytotoxicity of GP and GP-AuNPs were evaluated. The AuNPs exhibited a surface plasmon resonance at 536 nm, confirming the successful synthesis of nanoparticles, with a hydrodynamic size of 127.20 nm and a core size of 39.51 nm. The GP-AuNPs showed enhanced anti-gonococcal activity compared to GP with a minimum inhibitory concentration (MIC) of 10.40 and 46.70 μg/mL, respectively. Cytotoxicity was evaluated on human keratinocytes (HaCaT), human monocytes (THP-1), and STD-related human cervical adenocarcinoma (HeLa), with GP-AuNPs exhibiting fifty percent inhibitory concentrations (IC<sub>50</sub>) of 22.12 ± 0.52, 27.53 ± 6.02, and >38.96 μg/mL, respectively. In contrast, GP showed IC<sub>50</sub> values > 400 μg/mL against all tested cell lines. These findings indicate that GP-AuNPs exhibit significant anti-gonococcal activity with greater selectivity for <em>Neisseria gonorrhoeae</em> over non-cancerous (HaCaT and THP-1) cells, as evidenced by selectivity indices (SIs) > 2. These findings suggest that both GP and GP-AuNP possess potential as lead candidates for the treatment of gonorrhoea. Their limited antiproliferative activity against HeLa cells (SI < 0.7) indicates they are unsuitable for treating STD-associated cervical cancers. To the best of our knowledge, no published studies have investigated the effect of plant-synthesized nanoparticles on their activity against <em>N. gonorrhoeae</em>; therefore, this is the first use of GP-AuNPs against <em>N. gonorrhoeae</em>, advancing plant-based nanomedicine for STDs.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 107977"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980900","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}
Hong-Bo Wang , Zhe-Wen Lu , Pu Chen , Hai-Bo Mao , Li Jing
{"title":"Phosphatidylserine-modified extracellular vesicles encapsulating prednisolone for targeted drug delivery to pulmonary macrophages in acute lung injury","authors":"Hong-Bo Wang , Zhe-Wen Lu , Pu Chen , Hai-Bo Mao , Li Jing","doi":"10.1016/j.jddst.2026.107997","DOIUrl":"10.1016/j.jddst.2026.107997","url":null,"abstract":"<div><div>Acute lung injury (ALI) remains a significant challenge in clinical medicine, characterized by severe inflammation and progressive tissue damage that demand innovative therapeutic solutions. Extracellular vesicles (EVs), derived from macrophages, have emerged as promising drug delivery vehicles due to their biocompatibility and inherent targeting properties. Building on this foundation, our study explores the development of phosphatidylserine-modified EVs (PS-EVs) encapsulating prednisolone (Pre) to enhance pulmonary macrophage targeting and mitigate inflammation in ALI. The core focus of this research was to address the limitations of conventional ALI treatments, including insufficient drug accumulation in inflamed lung tissues and systemic side effects. Here, we show that PS-EVs@Pre exhibit superior targeting ability and sustained drug release, resulting in significantly improved therapeutic efficacy and reduced pulmonary inflammation in ALI mouse models. Our findings not only validate the hypothesis that PS modification enhances macrophage-specific targeting but also highlight how this approach updates current drug delivery paradigms by achieving localized therapy with minimal systemic toxicity. These results advance the field of targeted drug delivery systems and open new avenues for applying EV-based therapies in other inflammatory diseases.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 107997"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924216","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}
Antoinette G. Naeem , Diana M.F. Hanna , Haidy E. Michel , Dina O. Helal , Ebtehal El-Demerdash
{"title":"Intranasal calcitriol-loaded PLGA nanoparticles attenuate doxorubicin-induced cognitive impairment in rats via cGAS/STING and endoplasmic reticulum stress crosstalk","authors":"Antoinette G. Naeem , Diana M.F. Hanna , Haidy E. Michel , Dina O. Helal , Ebtehal El-Demerdash","doi":"10.1016/j.jddst.2026.108019","DOIUrl":"10.1016/j.jddst.2026.108019","url":null,"abstract":"<div><div>Doxorubicin (DOX) therapy results in cognitive impairment, known as “chemobrain”. Calcitriol (CAL) confers neuroprotection in many neuropathologies. Our objective was to develop a nose-to-brain nanocarrier-based delivery system of CAL for enhanced brain targeting and efficacy. CAL was loaded in poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) using the nanoprecipitation technique. Effects of formulation parameters on NPs physicochemical properties were evaluated. The neuroprotective effect of oral CAL solution (100 ng/kg/day) or intranasal CAL solution or CAL-NPs (30 ng/kg/day) was assessed in DOX-induced chemobrain rat model by neurobehavioral, histopathological, and biochemical assessments. CAL-NPs composed of 10 mg PLGA, 0.1 % Tween® 80 and 30 μg CAL were optimum for nose-to-brain delivery with particle size, polydispersity index, zeta potential, and entrapment efficiency of 164 ± 5.47 nm, 0.18 ± 0.02, −18.3 ± 0.6 mV, and 51.39 ± 1.53 %, respectively. Transmission electron microscope imaging confirmed the formation of spherical particles, and <em>in vitro</em> drug release showed a biphasic pattern with sustained drug release up to one week. Intranasal CAL treatment enhanced cognition, restored hippocampal histoarchitecture, and suppressed acetylcholinesterase activity. CAL hindered hippocampal neuroinflammation by enhancing sirtuin (SIRT) 1 expression and mitigating the cGAS/STING/p-TBK-1/NF-κB p65 axis and its effector cytokines. In addition, it suppressed p-IRE-1α/XBP-1s endoplasmic reticulum stress axis and its downstream pro-apoptotic CCAAT/enhancer binding protein homologous (CHOP) and caspase-3. Collectively, intranasal administration of CAL, particularly <em>via</em> PLGA NPs, enhanced CAL neuroprotective effect at one-third the oral dose, suggesting the potential use of CAL-NPs as a promising nose-to-brain delivery system for mitigation of DOX-induced chemobrain.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108019"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074416","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}
Huanfan He , Chengke Zhao , Jiayu Li, Xiaojing Pei, Hong Meng, Ze Zhang
{"title":"Hyaluronic acid-modified cationic nanoemulsion prepared by electrostatic self-assembly for improved specific targeting of keratinocytes and enhanced barrier repair efficacy","authors":"Huanfan He , Chengke Zhao , Jiayu Li, Xiaojing Pei, Hong Meng, Ze Zhang","doi":"10.1016/j.jddst.2026.108063","DOIUrl":"10.1016/j.jddst.2026.108063","url":null,"abstract":"<div><div>The expression of the Cluster of Differentiation 44 (CD44) receptor on the surface of keratinocytes provides a programmable target for localised precision drug delivery in the skin<strong>.</strong> The development of hyaluronic acid surface-modified ceramide cationic nanoemulsions (HA-CER-CNE) was based on electrostatic self-assembly between anionic hyaluronic acid (HA) and cationic ceramide nanoemulsions (CER-CNE). This carrier combines three functions: receptor-ligand-mediated endocytosis, high drug-loading capacity, and barrier repair. The subject under discussion here is an advancement on traditional ceramide formulations. The latter are limited by short skin retention times, low bioavailability, and unclear target specificity. The study found that HA-CER-CNE was significantly more endocytosed by HaCaT cells than CER-CNE. This was due to the specific binding of HA to the CD44 receptor, which was confirmed by confocal laser scanning microscopy (CLSM). An in vitro skin retention test demonstrated a 1.17-fold and 2.29-fold increase in skin retention of ceramide NP with HA-CER-CNE in comparison with CER-CNE and CER-suspension at 24 h. Furthermore, a cell scratch assay was employed to ascertain that HA-CER-CNE can further improve barrier damage. The cell migration rate of the HA-CER-CNE sample was 76.81 %, in comparison to 58.59 % for the CER-CNE sample. This indicates an enhancement of cell migration of 31.10 % in the former sample. The efficacy evaluation of HA-CER-CNE demonstrated that, incompared to CER-CNE and CER-suspension, HA-CER-CNE enhanced skin hydration by 1.62-fold and 4.13-fold, respectively, and reduced transdermal water loss (TEWL) by 1.75-fold and 4.23-fold, respectively, over a period of seven days. The findings demonstrate that HA-CER-CNE achieves precise delivery and retention of ceramides via a CD44-targeting strategy, exhibiting dual properties as both a drug carrier and bioactive agent.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108063"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073703","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}