Journal of Drug Delivery Science and Technology最新文献

{"title":"Synergistic cytotoxicity of paclitaxel-loaded liposomes and epigallocatechin-3-gallate in MCF-7 breast cancer cells: An in vitro nanotechnology-enhanced approach","authors":"Thanaa Ibrahim Shalaby ,&nbsp;Muhammad Alaa Eldeen ,&nbsp;Mohamed A. Akl ,&nbsp;Hagar Ahmed Hassanein Ibrahim ,&nbsp;Nivan Mahmoud Fekry ,&nbsp;Dalal Sulaiman Alshaya ,&nbsp;Eman Fayad ,&nbsp;Gehan A.M. Khodear","doi":"10.1016/j.jddst.2026.108007","DOIUrl":"10.1016/j.jddst.2026.108007","url":null,"abstract":"<div><div>Breast cancer (BC) remains a major global health burden. Although paclitaxel (PTX) is a clinically effective chemotherapeutic agent, its utility is constrained by poor aqueous solubility and dose-limiting toxicities associated with conventional formulations. Nanotechnology, specifically liposomal encapsulation, offers a promising solution to enhance drug delivery and reduce toxicity. Accordingly, we aimed to evaluate the therapeutic efficacy of a combined regimen of PTX-encapsulated nanoliposomes (L-PTX) and the natural compound epigallocatechin-3-gallate (EGCG) on the BC cell line, MCF-7. L-PTX, fabricated via the thin-film hydration method, was characterized and demonstrated a high encapsulation efficiency (EE) of 90 %, an average size of 345 nm, and a stable zeta potential (ζ) of −22 mV. In cytotoxicity assays, L-PTX was significantly more potent than free PTX (IC₅₀ at 72 h: 70 μg/mL vs. 100 μg/mL). Co-administration of L-PTX and EGCG yielded a synergistic effect, further lowering the IC₅₀ to 40 μg/mL (PTX concentration). Apoptosis assays confirmed that the combination treatment significantly induced oxidative stress (534.7 % increase in GSH), elevated caspase-3 activity (3.1-fold increase), and enhanced membrane damage (201.5 % increase in LDH), alongside notable DNA fragmentation. These findings suggest that combining L-PTX with EGCG provides a highly effective strategy for enhancing PTX therapeutic potency in BC cells while potentially mitigating the adverse effects of conventional PTX formulations. Future studies are warranted to validate this mechanism in drug-resistant cell lines (as <strong>MCF-7/ADR</strong>).</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108007"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035415","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":"Development of hydrolytically stable γ-cyclodextrin-based microparticles derived from MOFs for sustained pulmonary drug delivery","authors":"Caifen Wang ,&nbsp;Guoqing Zhang ,&nbsp;Qin Nie ,&nbsp;Ningning Peng ,&nbsp;Li Wu ,&nbsp;Xiaohong Ren ,&nbsp;Qian Wu ,&nbsp;Mubarak G. Bello ,&nbsp;Guanghong Xu ,&nbsp;Rui Yang ,&nbsp;Jiwen Zhang ,&nbsp;Lixin Sun","doi":"10.1016/j.jddst.2026.108064","DOIUrl":"10.1016/j.jddst.2026.108064","url":null,"abstract":"<div><div>Chronic lung diseases remain challenging to treat due to inefficient drug delivery and rapid clearance from the respiratory tract. In this study, covalently crosslinked γ-cyclodextrin particles (CDPs) were synthesized from γ-cyclodextrin metal–organic frameworks (MOFs) via esterification with diphenyl carbonate. The obtained CDPs exhibited a uniform particle size (D₅₀ = 1.19 μm) and a crosslinking degree of approximately 4. Structural and physicochemical characterizations indicated the successful covalent transformation, preserved internal cavities, and enhanced aqueous stability. Dexamethasone (DEX) was encapsulated within CDPs to form DEX@CDP complexes. Next generation impactor testing revealed superior aerosolization with fine particle fractions of 85.36 % (CDP) and 67.01 % (DEX), ensuring efficient deposition in the deep lung region. <em>In vitro</em> release studies showed sustained release, with less than 31 % of DEX released over 24 h. <em>In vivo</em> pharmacokinetic analysis demonstrated that DEX@CDP doubled mean residence time (MRT) and elimination half-life (t_1/2) compared to inhaled DEX@MOF and intragastric DEX. Furthermore, CDPs exhibited excellent cytocompatibility toward A549 and J774A.1 cells (20–500 μg/mL) and favorable <em>in vivo</em> biocompatibility. These results indicate that the hydrolytically stable, cavity-retaining CDPs derived from MOFs are promising inhalable carriers for efficient and sustained pulmonary drug delivery.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108064"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397306","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":"Folate receptor targeting amino modified Niobium MXene for the delivery of Doxorubicin to cancer cells","authors":"Vijayakumar G. Gayathri ,&nbsp;Gopika S. Kumar ,&nbsp;Anwar A. Palakkan ,&nbsp;Manisha Dasarath Wasake ,&nbsp;Jagadeesh Bayry ,&nbsp;P Abdul Rasheed","doi":"10.1016/j.jddst.2026.107989","DOIUrl":"10.1016/j.jddst.2026.107989","url":null,"abstract":"<div><div>This study investigates the amino-modified niobium carbide MXene (Nb₂CT_<em>x</em>) for the delivery of doxorubicin in cancer therapy. Ethylenediamine was employed to introduce amine groups onto the surface of Nb₂CT_<em>x</em> MXene nanosheets. The resulting amino-modified MXene was assessed for cytotoxicity and cellular uptake in hepatic, retinal, and cervical cell lines, where it exhibited minimal cytotoxicity and superior biocompatibility across a broad concentration range. Further, doxorubicin-conjugated MXene nanoparticles induced a clear, dose-dependent reduction in cell viability, indicating efficient drug release. Confocal microscopy analysis revealed a robust intracellular accumulation of doxorubicin in treated cells, while flow cytometry confirmed efficient uptake of the nanocarrier system in over 90 % of cells. To enhance tumor targeting and minimize off-target toxicity, folic acid was conjugated to the system to target the folate receptor, which is frequently overexpressed in cancer cells. The folate receptor-targeted nanocarrier system demonstrated significantly greater cytotoxicity than their non-targeted counterparts, even at nanogram concentrations, with the most pronounced effects observed in HeLa cells. Collectively, these findings highlight the potential of amino-modified MXene nanocarriers as a versatile platform for targeted chemotherapy, combining high drug-loading capacity with controlled drug release. Furthermore, this system holds promise for development into a theranostic platform integrating diagnosis and therapy. Also, the system can be readily adapted to incorporate additional therapeutic modalities, such as photothermal therapy or combination drug delivery, to achieve precise and effective cancer treatment with reduced off-target effects.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 107989"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980187","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":"Lurasidone hydrochloride nanomixed micelles in sublingual orodispersible tablets: in-Vitro and in-Vivo evaluation","authors":"Zahraa F. Diab ,&nbsp;Ahmed R. Fares ,&nbsp;Omaima N. El-Gazayerly ,&nbsp;Mohamed H.H. AbouGhaly","doi":"10.1016/j.jddst.2026.107999","DOIUrl":"10.1016/j.jddst.2026.107999","url":null,"abstract":"<div><div>Lurasidone hydrochloride (LH) is a second-generation antipsychotic drug that has poor aqueous solubility. It also suffers from hepatic first pass metabolism resulting in poor bioavailability. The aim of this study was to prepare LH nanomixed micelles (NMMs) to enhance its aqueous solubility. Preliminary studies showed that Soluplus® and Cremophor® EL (CrEL) can solubilize the drug and form LH NMMs that have desirable entrapment efficiency (EE%), saturated solubility, and particle size (PS). The selected optimum NMMs was further characterized by differential scanning calorimetry (DSC) and transmission electron microscopy (TEM). The selected system was then incorporated into sublingual orodispersible tablets (ODTs). Three ready-made orally disintegrating platforms (Galen IQ™721, Pearlitol Flash®, and Prosolv ODT®) were tested. Prosolv ODT® showed the best results regarding simulated wetting time (SWT), disintegration, and dissolution times. The optimum ODT formulation was then tested for <em>ex-vivo</em> permeability and <em>in-vivo</em> pharmacokinetics versus the oral commercially available tablets Elbaluran® 20 mg. The prepared ODTs showed enhanced permeability, higher and faster peak plasma concentration, and more distribution into the brain. Statistical analysis of pharmacokinetic parameters such as C_max and t_max showed that ODT T11 is superior to Elbaluran® 20 mg. AUC_0-t, AUC_0-∞, MRT, and brain distribution showed higher values for the optimum formula however the differences between the two groups were non-significant. Therefore, it can be concluded that Soluplus ®/CrEl NMMs are promising in enhancing LH aqueous solubility. Besides, the prepared ODTs showed higher <em>in-vivo</em> relative bioavailability (RB) compared to the marketed oral tablets.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 107999"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980385","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":"Multifunctional fluorescent magnetic molecularly imprinted polymer for curcumin delivery: in vivo wound healing, antibacterial activity, and in silico pharmacokinetic evaluation","authors":"Zeeshan Ali ,&nbsp;Nadeem Raza ,&nbsp;Muhammad Hayat ,&nbsp;Hafiz Muhammad Usman Abid ,&nbsp;Abdelmonaim Azzouz ,&nbsp;Bouchra Rossafi ,&nbsp;Imad Hammoudan ,&nbsp;Anis Ahmad Chaudhary ,&nbsp;Mohamed Khairy ,&nbsp;Mohamed Abdel-Megid","doi":"10.1016/j.jddst.2026.107980","DOIUrl":"10.1016/j.jddst.2026.107980","url":null,"abstract":"<div><div>Molecularly imprinted polymers (MIPs) stand out in various biomedical realms as potent and expanding nanoplatforms. This research employed a surface molecular imprinting approach<strong>,</strong> in which a polydopamine shell was polymerized around Fe₃O₄@SiO₂@FITC nanoparticles in the presence of curcumin (template)<strong>.</strong> After template removal, surface-exposed recognition sites complementary to curcumin were formed, confirming successful imprinting. The synthesized fluorescent magnetic MIPs (FMMIPs) exhibited significant drug loading capacity and responsiveness to magnetic fields, serving as efficient carriers for CUR delivery. Characterization of FMMIPs was executed through FTIR, SEM, TGA, XRD, vibrating sample magnetometry, and dynamic light scattering. The magnetization value of FMMIP was measured at 0.045 emu/g, underscoring its robust magnetic responsiveness to external fields. In-vivo studies for CUR loading and release unveiled that under tissue conditions (pH 5 and 41 °C) a maximal CUR release of 71.33 % occurred, following a sustained profile, compared to the standard physiological environment (pH 7.4 and 37 °C). In diabetic rats, treatment with FMMIP-CUR resulted in 97.55 % wound healing, surpassing the standard treatment with silver sulfadiazine. Histopathological evaluations further confirmed marked enhancements in re-epithelialization, fibroblast activity, and angiogenesis in diabetic wounds after 12 days of treatment. To explore the antibacterial potential of CUR, molecular docking and molecular dynamics (MD) simulations were conducted against <em>P. aeruginosa</em> (4KQR) and <em>S. aureus</em> (3Q8U) targets. CUR exhibited stronger binding affinities compared to ciprofloxacin, forming stable hydrogen bonds and hydrophobic interactions with key residues. The MD simulations over 100 ns revealed greater interaction stability and diversity in the 4KQR–CUR complex, while CUR's interaction with 3Q8U was more dynamic. ADMET predictions confirmed favorable pharmacokinetics and drug-likeness for both compounds, with CUR showing good oral bioavailability, moderate solubility, low toxicity, and acceptable metabolic profiles. The adsorption of CUR onto FMMIPs followed the Freundlich isotherm model (R² = 0.991) indicating heterogeneous surface binding and the presence of multiple adsorption sites with varying affinities. These results demonstrate FMMIP nanocarrier's potential as a viable option for antidiabetic drug delivery systems.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 107980"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980389","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":"Plasma-assisted electrospinning of functional nanofibers: Solution and surface nanoengineering for biomedical applications","authors":"Jesús Quezada-Urbina ,&nbsp;Edna Vázquez-Vélez ,&nbsp;Carlos J. Villagómez ,&nbsp;Josselyne Transito-Medina ,&nbsp;Victor M. Castaño","doi":"10.1016/j.jddst.2026.108024","DOIUrl":"10.1016/j.jddst.2026.108024","url":null,"abstract":"<div><div>Electrospun nanofibers have attracted considerable attention due to their unique physicochemical properties and broad range of applications, particularly in biomedical applications. Non-Thermal Plasma (NTP) treatment has emerged as a versatile tool for tailoring both the properties of polymer solutions before electrospinning and the characteristics of the resulting nanofibers. When applied to polymer solutions, NTP alters essential parameters such as viscosity, ionic conductivity, and surface tension through dipole-dipole and ion-dipole interactions between plasma ions and solvent or polymer molecules. These interactions facilitate the expansion of polymer coils, thereby improving electrospinnability. As a result, the nanofibers produced exhibit superior morphological, mechanical, and physicochemical properties. NTP treatment enhances the performance of nanofiber surfaces by increasing hydrophilicity, biocompatibility, and surface reactivity. Nevertheless, optimizing plasma parameters to achieve reproducible results remains a significant challenge. This article reviews recent advancements in NTP-assisted electrospinning, highlighting its potential to produce functional nanofibers for biomedical applications, including bioactive scaffolds, antimicrobial dressings, and controlled drug-delivery systems. Furthermore, it positions NTP as an influential tool for regenerative medicine and wound healing.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108024"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035341","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":"External electric field modulation of polyelectrolyte complex nanoparticles for vaccine delivery","authors":"Rasim Masimov ,&nbsp;Matija Tomšič ,&nbsp;Ellen K. Wasan","doi":"10.1016/j.jddst.2026.108031","DOIUrl":"10.1016/j.jddst.2026.108031","url":null,"abstract":"<div><div>Polyelectrolyte complex nanoparticles (PECNs) are widely used as carrier systems, particularly for delivering nucleic acids and proteins. Their unique characteristics have led to extensive research into their potential as vaccine delivery platforms. Since PECNs form through electrostatic interactions, various solution and physical parameters can influence their structure during and after fabrication. We discovered that applying an electric voltage affects the physicochemical properties of PECNs comprised of chitosan complexed to a polyelectrolyte vaccine adjuvant. Subsequently, we explored the effect of voltage application on their physical properties and performance as vaccine nanocarriers. The nanoparticles were prepared using microfluidic mixing, with the physicochemical properties of these formulations assessed both before and after exposure to electric voltage. Results showed that exposure to electric voltage can alter the physicochemical properties of PECNs, subsequently impacting their <em>in vitro</em> efficacy. This also emphasizes the importance of carefully considering the sequential order of particle size and zeta potential determinations, as these parameters are derived from DLS and electrophoretic mobility measurements, respectively, and the latter can influence the physicochemical properties of PECNs.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108031"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035411","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":"In silico–designed peptide targeting MDR1 (P-gp) restores chemosensitivity in colorectal cancer via chitosan nanoparticle delivery","authors":"Hande Maden ,&nbsp;Hilal Calik ,&nbsp;Rabia Yilmaz Ozturk ,&nbsp;Selcen Ari Yuka ,&nbsp;Betül Zehra Temur ,&nbsp;Özge Can ,&nbsp;Gizem Dinler Doğanay ,&nbsp;Rabia Cakir","doi":"10.1016/j.jddst.2026.108003","DOIUrl":"10.1016/j.jddst.2026.108003","url":null,"abstract":"<div><div>Colorectal cancer is the second most common cause of cancer-related deaths worldwide. Most of these deaths are due to failure of chemotherapy caused by drug resistance and resulting tumor recurrence. Therefore, overcoming drug resistance is crucial for the successful treatment of colorectal cancer. In this study, the P5S3 peptide selected by bioinformatics analysis for inhibiting drug resistance and the 5-FU drug were loaded into chitosan nanoparticles and investigated <em>in vitro</em> on drug-resistant colorectal cancer cells. Firstly, P5S3 was identified as a peptide inhibitor by MDR1 binding site-specific molecular docking analyses and <em>in silico</em> prediction of biological and physicochemical properties. The peptide was synthesized using the solid phase synthesis method and characterized by RP-HPLC and LC-MS/MS. Chitosan nanoparticles loaded with 5-FU and P5S3 (5-FU/P5S3@CSNPs) were synthesized using an ionic gelation method and characterized using a ZetaSizer, FT-IR, FE-SEM, and UV–Vis. The 5-FU/P5S3@CSNPs were approximately 110 nm in size and spherical in shape, and had a good encapsulation efficiency and loading capacity. Furthermore, drug resistance was conferred to sensitive HCT-116 cells (HCT-116/FU) that were continuously exposed to 5-FU, and the development of drug resistance was confirmed by qPCR. The effect of 5-FU/P5S3@CSNPs on cell viability in HCT-116/FU cells and their inhibitory activities on MDR1 drug efflux pumps were analyzed by XTT and accumulation assay, respectively. Our results demonstrate that the 5-FU/P5S3@CSNPs had high anticancer potential against HCT-116/FU cells and high inhibition ability of MDR1. In conclusion, our findings suggest that 5-FU/P5S3@CSNPs offer a promising approach for the treatment of resistant colorectal cancer.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108003"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035413","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":"Evaluation of multi-port needles for enhanced intramuscular drug delivery via experimental and CFD models","authors":"Allexia Passos Souza,&nbsp;Jeremy Marston","doi":"10.1016/j.jddst.2026.108022","DOIUrl":"10.1016/j.jddst.2026.108022","url":null,"abstract":"<div><div>Intra-muscular (IM) injection via hypodermic needle and syringe is the most common delivery method of vaccines due to the muscle tissue ability to receive large volumes, high degree of vascularization, and tolerance of needle insertion. When injections are augmented with enabling technologies such as electroporation (EP), the drug dispersion zone becomes an important consideration since it should match with the electric field generated by the EP device. Herein, we sought to modify the flow from a standard hypodermic by implementing multiple side-ports along the length of the needle. We evaluated the flow in these side-port designs using CFD simulations and experimental validation. Our results indicate that low flow rates (<span><math><mrow><mi>Q</mi><mo>&lt;</mo><mn>10</mn></mrow></math></span> mL/min, <span><math><mrow><mi>R</mi><mi>e</mi><mo>=</mo><mn>4</mn><mi>ρ</mi><mi>Q</mi><mo>/</mo><mi>π</mi><mi>d</mi><mi>μ</mi><mo>≲</mo><mn>500</mn></mrow></math></span>) result in non-uniform flow distribution, while higher flow rates (<span><math><mrow><mi>Q</mi><mo>≳</mo><mn>15</mn></mrow></math></span> mL/min, <span><math><mrow><mi>R</mi><mi>e</mi><mo>≳</mo><mn>769</mn></mrow></math></span>) result in near-uniform distribution of flow along all the side-ports, potentially creating superior drug dispersion pattern along the needle length for improved cellular uptake with EP.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108022"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035463","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":"Choline-retinoic acid ionic liquid as a potential therapy agent for acute promyelocytic leukemia","authors":"Hongyu Zhu ,&nbsp;Liuyang Wang ,&nbsp;Jingyang Zhao ,&nbsp;Zhiguo Su ,&nbsp;Kiichi Sato ,&nbsp;Xiaoyi Wang ,&nbsp;Songping Zhang","doi":"10.1016/j.jddst.2026.108039","DOIUrl":"10.1016/j.jddst.2026.108039","url":null,"abstract":"<div><div>All-trans retinoic acid (Ra)-mediated differentiation therapy remains the first-line treatment for acute promyelocytic leukemia (APL). However, Ra must be administered orally due to its extremely poor aqueous solubility. The absorption of Ra is influenced by various factors, which can result in variable bioavailability and, consequently, variable therapeutic effects. Accordingly, the development of a parenteral Ra formulation is highly demanded. In the current study, Choline-retinoic acid ([Cho][Ra]), which significantly improved the water solubility of Ra, was systemically evaluated as the pro-differentiation and pro-apoptosis agent for APL cells. <em>In vitro</em> cellular studies demonstrate that compared to Ra, [Cho][Ra] induced a more pronounced G0-G1 phase cell cycle arrest, leading to a greater inhibition of cell proliferation. Concurrently, it also promoted a higher percentage of cells to undergo differentiation. Furthermore, [Cho][Ra] showed superior efficacy in inducing late-stage apoptosis, which was associated with a more severe loss of mitochondrial membrane potential. [Cho][Ra] treatment also induced higher reactive oxygen species (ROS) levels, which suggests that ROS generation may be a key mechanistic contributor to both cell apoptosis and differentiation. These findings suggest that [Cho][Ra] could be a promising alternative to Ra, overcoming the solubility limitations and improving its efficacy in treating leukemia.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108039"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035465","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}