Journal of Drug Delivery Science and Technology最新文献

{"title":"Formulation matters: Assessment of the correlation between mucoadhesiveness and type of chitosan formulation for vaginal application","authors":"Silje Mork,&nbsp;Charlotte Eilertsen,&nbsp;Nataša Škalko-Basnet,&nbsp;May Wenche Jøraholmen","doi":"10.1016/j.jddst.2025.107564","DOIUrl":"10.1016/j.jddst.2025.107564","url":null,"abstract":"<div><div>Localized vaginal drug delivery can offer safer and more effective treatment options for various conditions, also for pregnant women. However, inadequate retention of formulation in the vaginal cavity hinders efficient treatment. Mucoadhesive drug delivery systems using mucoadhesive polymers may be a promising solution. In this work, the biopolymer chitosan was chosen for its well documented mucoadhesive properties, favorable biopharmaceutical profile, and low toxicity. However, its mucoadhesive abilities may depend on how chitosan is formulated. This study therefore focused on two distinct chitosan formulations, chitosan-coated liposomes and liposomes-in-chitosan hydrogel, to compare mucoadhesiveness across formulations. Additionally, two chitosan molecular weights (LMW and MMW) and four concentrations (0.1 %, 0.3 %, 0.6 % and 1.0 %) were examined, whilst considering site-specific factors like pH, biological fluids, and temperature. The formulations were characterized, and their mucoadhesive behavior evaluated by monitoring changes in viscosity and zeta potential upon mixing with mucin. Liposomes averaged 135 nm in size with a zeta potential of −2.78 mV, where the charge increased with chitosan coating or incorporation into chitosan hydrogel. Both chitosan-coated liposomes and liposomes-in-hydrogel exhibited rheological properties suitable for vaginal application. Mucoadhesion indeed varied based on the formulation, chitosan concentration, molecular weight, pH, and temperature. Notably, liposomes-in-hydrogel formulations demonstrated superior mucoadhesive potential. These findings emphasize the importance of formulation design and environmental factors in optimizing mucoadhesion.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107564"},"PeriodicalIF":4.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154546","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":"High-purity cochleates engineered with DOTAP: Unlocking new potential for drug delivery","authors":"Nishtha Thakur,&nbsp;Shuddhodana,&nbsp;Zaher Judeh","doi":"10.1016/j.jddst.2025.107557","DOIUrl":"10.1016/j.jddst.2025.107557","url":null,"abstract":"<div><div>Cochleates are multilamellar lipid–calcium precipitates with potential for oral delivery of poorly soluble or irritant drugs, but their heterogeneity has limited translation. Here, we report the engineering of highly pure, structurally uniform cochleates using a cationic lipid (DOTAP) in combination with anionic phospholipids (DOPS, DMPS). CAP (capsaicin) was selected as a model drug due to its poor solubility, instability, and gastrointestinal side effects. DOTAP-containing cochleates (H) displayed well-defined rod-like morphology, reduced aggregation, and enhanced colloidal stability compared to conventional formulations (A–G). Physicochemical analysis (FE-SEM, SAXS, DSC, FTIR) confirmed strong CAP–lipid interactions, reduced crystallinity, and improved bilayer ordering. Encapsulation efficiency reached 93.3 % with loading of 196 mg/g, markedly higher than typical nanocarriers. In-vitro release showed suppressed burst effect and sustained diffusion-controlled release over 94 h, with cochleates H exhibiting the slowest release kinetics. Stability studies demonstrated excellent drug retention at physiological pH and moderate temperatures. Together, these findings establish DOTAP-engineered cochleates as a robust platform for oral delivery, offering high purity, reproducibility, and translational promise for hydrophobic or irritant drugs.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107557"},"PeriodicalIF":4.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154550","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":"Incorporating fluid-structure interactions for modelling of pyramidal hollow microneedles for transdermal drug delivery","authors":"Rahul Nadda ,&nbsp;Ravi Prakash ,&nbsp;Diganta Bhusan Das ,&nbsp;Ryan F. Donnelly","doi":"10.1016/j.jddst.2025.107561","DOIUrl":"10.1016/j.jddst.2025.107561","url":null,"abstract":"<div><div>Hollow microneedles (HMNs) have gained significant attention as a potential alternative to traditional hypodermic needles for delivering drugs through the skin. The rational selection of the HMN geometry and materials is essential for balancing the MN's mechanical stability and efficient drug delivery. In addressing this, the current study aims to develop a numerical model for fluid-structure interactions (FSI) in hollow pyramidal-shaped MNs where HMNs made from two polymers (polylactic acid (PLA) and polyglycolic acid (PGA)) and one metal (stainless steel (SS)) are considered. Finite element (FE) simulations have been performed with COMSOL 6.2 Multiphysics to determine the effect of MN design parameters such as wall thickness, pitch, channel diameter, and dual-zone MN structure (different MN lengths) on fluid flow and von Mises stress distribution in the HMNs. The FSI analysis has been conducted for a laminar flow of water-fentanyl mixture as a model fluid. The findings revealed that raising the inlet pressure from 10 kPa to 30 kPa at the HMN entrance increases the flow rate to 0.005 μl/s, velocity 0.003 m/s, and total drug flux by 248.63 %. As expected, SS demonstrated the lowest von Mises stress (13 213 N/m²) while PLA and PGA exhibited a decrease in the stress level as the HMN wall thickness increased. Increasing the MN pitch from 400 μm to 1200 μm reduced skin pore pressure by 72 % and enhanced drug concentration by 11.4 %. The dual-zone MN arrangement, combining shorter and longer needles, improved the HMN penetration and led to a 90.8 % increase in overall flux. These findings provide a foundation for optimising HMN designs, ensuring a balance between mechanical stability and improved transdermal drug diffusion for clinical applications.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107561"},"PeriodicalIF":4.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154551","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":"Ticagrelor-loaded lipid nanocapsules as a promising nebulizable system for lung cancer: in-vitro characterization, 131I radiolabeling and in-vivo biodistribution","authors":"Mohamed Fawzi Kabil ,&nbsp;Khaled M. Attallah ,&nbsp;Ibrahim El-sherbiny ,&nbsp;Maha Nasr","doi":"10.1016/j.jddst.2025.107560","DOIUrl":"10.1016/j.jddst.2025.107560","url":null,"abstract":"<div><div>This study investigates the encapsulation of Ticagrelor (Tic) within lipid nanocapsules (LNCs) as a potential nebulizable drug delivery system for the treatment of lung cancer. The prepared LNCs were evaluated through <em>in-vitro</em> characterization, including dynamic light scattering (DLS) and surface morphology. Additionally, an <em>in-vivo</em> biodistribution study was conducted after radiolabeling the selected Tic-LNCs with iodine-131 (¹³¹I) to assess their distribution and deposition within various body organs. Results indicated that the Tic-LNCs had a particle size ranging from 137.5 ± 0.4 nm to 340.15 ± 17.3 nm. The <em>in-vitro</em> cytotoxicity using the MTT assay showed that Tic-LNCs exerted a substantial inhibitory effect against A549 lung cancer cells, with IC₅₀ values of Tic and Tic-LNCs being 21.72 ± 1.22 μg/mL and 3.42 ± 0.103 μg/mL, respectively. The <em>in-vivo</em> biodistribution study revealed that the ¹³¹I-Tic-LNCs demonstrated significantly better lung uptake compared to the parent drug solution. The lung-to-blood ratio for the Tic-LNCs reached a maximum of 2.67 within 4 h after administration. In conclusion, the nebulizable Tic-LNCs nanosystem holds promise as a targeted pulmonary drug delivery system for the treatment of lung cancer.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107560"},"PeriodicalIF":4.9,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154564","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":"Polycaprolactone nanoparticles for targeted and prolonged topical delivery of azithromycin to pilosebaceous follicles","authors":"Breno N. Matos,&nbsp;José L.L. Alcântara,&nbsp;Paula M. Oliveira,&nbsp;Lucas Cantalovo,&nbsp;Camila O. Cardoso,&nbsp;Marcilio Cunha-Filho,&nbsp;Tais Gratieri,&nbsp;Guilherme M. Gelfuso","doi":"10.1016/j.jddst.2025.107559","DOIUrl":"10.1016/j.jddst.2025.107559","url":null,"abstract":"<div><div>Topical administration of antibiotics for localized skin infections offers advantages over systemic therapies, including reduced side effects and minimized antimicrobial resistance. However, when using azithromycin topically to treat acne, the low capacity of this potent antibiotic to reach the affected pilosebaceous units compromises therapy. This study aimed to develop azithromycin-loaded polymeric nanoparticles to enhance follicular targeting and improve topical drug delivery. Thermal analyses showed compatibility and miscibility between azithromycin and polycaprolactone. The polymeric nanoparticles produced by the nanoprecipitation method were spherical, monodisperse (158.3 ± 0.4 nm; PdI&lt;0.1), achieved an entrapment efficiency of 92.5 ± 0.1 % for azithromycin, and exhibited a sustained drug release profile over 12 h. They enhanced drug deposition in pilosebaceous follicles compared to the control drug solution over 24 h. Indeed, 43 ± 6 % of the drug was localized in follicles after 24 h of skin treatment–a fivefold (p &lt; 0.05) increase in the targeting factor relative to control. The nanodispersion was also demonstrated to be non-irritant. In conclusion, the polycaprolactone nanoparticles effectively targeted and prolonged azithromycin delivery to hair follicles while minimizing systemic exposure, offering a promising strategy for the topical treatment of follicle-associated infections.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107559"},"PeriodicalIF":4.9,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095528","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":"Functionalized carbon nanoparticles for plumbagin delivery: Physicochemical characterization, antibacterial activity, and molecular docking","authors":"Chunshuang Li ,&nbsp;Ming Lu ,&nbsp;Ze Yao ,&nbsp;Ruobing Liu ,&nbsp;Ding Lu ,&nbsp;Tenglong Ma ,&nbsp;Xiang Li ,&nbsp;Hui Shang ,&nbsp;Songtao Bie","doi":"10.1016/j.jddst.2025.107551","DOIUrl":"10.1016/j.jddst.2025.107551","url":null,"abstract":"<div><div>Bacterial biofilms play a critical role in chronic wound infections by significantly delaying wound healing. <em>Staphylococcus aureus</em>, one of the most prevalent biofilm-forming pathogens, secretes extracellular polymeric substances that effectively protect it from host immune defenses and antibiotic treatments. To address this challenge, nanoscale antibacterial strategies have attracted increasing attention in recent years. By encapsulating antibacterial agents within nanocarriers, drug penetration into biofilms can be enhanced, thereby improving bioavailability. In this study, we synthesized bovine serum albumin-functionalized carbon nanoparticles (CB) via the functionalization method. The antibacterial agent plumbagin (PLB) was subsequently loaded onto them to form nanocomposites (CB-PLB). We comprehensively characterized their physicochemical properties, including particle size, polydispersity index, morphology, drug-loading efficiency, thermal behavior (differential scanning calorimetry, DSC), crystallinity (X-ray diffraction, XRD), spectroscopic features, solubility, and <em>in vitro</em> drug-release profiles. Specifically, we examined the impact of CB-PLB on both biofilm formation and established mature biofilms of <em>Staphylococcus aureus</em>. In comparison to PLB, CB-PLB showed better antibacterial and anti-biofilm activity against formed and matured biofilm using crystal violet staining and XTT assay. High-content screening imaging analyses confirmed that CB-PLB exerted potent disruptive effects, including reduction of biomass, mean thickness, and alteration of biofilm roughness. Furthermore, molecular docking analysis confirmed specific interactions among carbon nanoparticles (CNP), PLB, and bovine serum albumin (BSA). These findings highlight the synergistic interaction between CB and PLB, suggesting that CB is a promising nanocarrier for hydrophobic antibacterial agents.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107551"},"PeriodicalIF":4.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095513","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 comparison of charged and uncharged stabilizers on the loading of hydrophilic low and high molecular weight synthetic charged molecules in the LeciPlex® system","authors":"Harshali Dhaygude ,&nbsp;Saurabh Katawale ,&nbsp;Shivali Tank ,&nbsp;René Holm ,&nbsp;Sanket Shah ,&nbsp;Ujwala Shinde ,&nbsp;Supriya Shidhaye ,&nbsp;Mangal Nagarsenker","doi":"10.1016/j.jddst.2025.107556","DOIUrl":"10.1016/j.jddst.2025.107556","url":null,"abstract":"<div><div>The present investigation aims to evaluate the loading of hydrophilic molecules with varying physicochemical properties in LeciPlex®. Polysorbate 80, taurocholate, and dioctadecyldimethylammonium bromide (DODAB) were used to prepare non-ionic, anionic and cationic LeciPlex® respectively, and their interactions with two model hydrophilic compounds differing in molecular weight, surface charge and structural features are explored. A negatively charged peptide, daptomycin was encapsulated via passive loading, while a positively charged amphipathic base, acridine orange required a remote loading. All formulations were characterized for particle size, zeta potential, and entrapment efficiency. Daptomycin and acridine orange LeciPlex® were further characterized by transmission electron microscopy (TEM) and evaluated for in vitro release profiles by dialysis bag method. In addition to the above characterizations, daptomycin-loaded LeciPlex® was further evaluated for thermal behavior using differential scanning calorimetry (DSC), antimicrobial efficacy via the resazurin assay, haemocompatibility and physicochemical stability. The type of stabilizer and phospholipid concentration directly influenced the particle size and entrapment of daptomycin LeciPlex®. The average particle size of daptomycin-loaded LeciPlex® was lower compared to the acridine orange-loaded LeciPlex®. Acridine orange entrapment (55–80 %) increased with cholesterol incorporation. TEM revealed uni or oligo lamellar vesicles. DSC confirmed the interaction of daptomycin with lipid in all three daptomycin-LeciPlex® systems. Both daptomycin and acridine orange LeciPlex® systems demonstrated sustained release profiles and improved stability. Daptomycin LeciPlex® showed comparable antimicrobial efficacy to that of the solution and exhibited minimal haemolysis. Present study demonstrated the successful encapsulation of structurally diverse hydrophilic molecules into LeciPlex® using a simplified and scalable approach.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107556"},"PeriodicalIF":4.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219844","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":"Electrospun mucoadhesive nanofibrous films for intranasal delivery of propranolol hydrochloride for migraine prophylaxis","authors":"Konstantina Chachlioutaki ,&nbsp;Melpomeni Liogka ,&nbsp;Paraskevi M. Petinari ,&nbsp;Savvas Koltsakidis ,&nbsp;Aliki Papadimitriou-Tsantarliotou ,&nbsp;Chrysanthi Bekiari ,&nbsp;Ioannis S. Vizirianakis ,&nbsp;Dimitrios Tzetzis ,&nbsp;Nikolaos Bouropoulos ,&nbsp;Dimitrios G. Fatouros","doi":"10.1016/j.jddst.2025.107552","DOIUrl":"10.1016/j.jddst.2025.107552","url":null,"abstract":"<div><div>Migraine treatment failure is often associated with the delayed onset and variable efficacy of conventional oral medications, which are further limited by poor patient compliance due to gastrointestinal side effects and frequent dosing requirements. To address these challenges, a fast-disintegrating mucoadhesive nanofibrous film was developed for the intranasal administration of propranolol hydrochloride (PROP), a well-established migraine prophylactic agent. The electrospun films were formulated using rapidly dissolving pullulan and chitosan, known for its strong mucoadhesive properties, ensuring immediate drug availability at the site of action and promoting permeation through the nasal epithelium via the nose-to-brain delivery route, thereby bypassing first-pass metabolism. The films demonstrated sufficient elasticity, allowing them to be cut and rolled into solid dosage forms for convenient intranasal administration. Upon hydration, the films transitioned into a gel-like state, as confirmed by rheological studies conducted in simulated nasal electrolyte solution (SNES) at 35 °C<em>. In vitro</em> release studies in SNES revealed rapid PROP dissolution, while cytocompatibility was assessed using the Calu-3 cell line, showing dose-dependent effects likely influenced by the PROP concentration. Mucoadhesion studies indicated a significant enhancement of retention at the nasal mucosa, with higher chitosan concentrations contributing to improved drug residence and facilitated transport across the epithelium. To overcome the limitations of oral PROP administration, such as poor bioavailability and delayed onset of action, the proposed electrospun nanofiber films might offer a promising alternative for effective and patient-friendly migraine therapy via intranasal delivery.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107552"},"PeriodicalIF":4.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109529","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":"Biocompatible NiTiO3–Dopamine nanocomposites for combating drug-resistant pathogens through membrane disruption and oxidative stress","authors":"Indumathi Thangavelu ,&nbsp;Srinivas Tadepalli","doi":"10.1016/j.jddst.2025.107553","DOIUrl":"10.1016/j.jddst.2025.107553","url":null,"abstract":"<div><div>The rising threat of multidrug-resistant pathogens poses a challenge to public health. Highlighting the urgent need for novel antimicrobial agents, this study reports the synthesis of NiTiO₃ nanoparticles and dopamine-functionalized NiTiO₃ nanocomposites. Structural and elemental confirmation was obtained through XPS studies, which confirmed the presence of Ni²⁺ and Ti⁴⁺ in the nanocomposite, along with C 1s and O 1s peaks corresponding to dopamine coating. Photoluminescence spectra revealed that the NiTiO₃–dopamine nanocomposite exhibits notable green emission bands at 510, 518, and 527 nm which arises from deep-level recombination associated with complex oxygen-related defects like oxygen vacancies. The NiTiO₃-dopamine exhibited enhanced antimicrobial activity against <em>S. aureus</em>, <em>B. subtilis</em>, <em>K. pneumoniae</em>, <em>S. dysenteriae</em>, and <em>C. albicans</em>, compared to NiTiO₃ alone. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays further revealed that NiTiO₃–dopamine achieved MIC at 600 μg/mL and MBC at 1000 μg/mL for <em>K. pneumoniae</em>, outperforming pure NiTiO₃. ROS assays confirmed oxidative stress-mediated antimicrobial action, with ROS levels significantly quenched in the presence of histidine. SEM images of bacterial morphology showed extensive membrane disruption in NiTiO₃–dopamine treated cells. Furthermore, zebrafish embryo assays confirmed excellent biocompatibility of the NiTiO₃–dopamine nanocomposite, with normal development observed up to 72 h post fertilization.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107553"},"PeriodicalIF":4.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095512","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":"Machine learning models predict pH-responsive drug release from liver-targeted agarose-CMC-CeO2 nanocomposites: Liver-targeted antioxidant strike","authors":"Mehrab Pourmadabi ,&nbsp;Zahra Omrani ,&nbsp;Amir Doustgani ,&nbsp;Fatemeh Yazdian ,&nbsp;Mona Nourhashemi ,&nbsp;Tahmineh Ahmadi ,&nbsp;Abbas Rahdar ,&nbsp;Sonia Fathi-karkan ,&nbsp;Nasrin Valizadeh ,&nbsp;Luiz Fernando Romanholo Ferreira","doi":"10.1016/j.jddst.2025.107555","DOIUrl":"10.1016/j.jddst.2025.107555","url":null,"abstract":"<div><div>This research presents an innovative carboxymethyl cellulose/agarose/cerium oxide (CMC/Aga/CeO₂) nanocarrier for the pH-sensitive delivery of quercetin (QC) to hepatocellular carcinoma cells. The nanocarrier exhibited exceptional drug-loading proficiency, achieving 88.25 % entrapment efficiency and 51.00 % loading capacity, which was significantly enhanced by the use of CeO₂. The ideal physicochemical characteristics comprised a consistent hydrodynamic diameter of 193.48 nm and elevated colloidal stability (zeta potential: -61.6 mV). The system exhibited tumor-selective release kinetics, discharging 98 % of QC at an acidic tumor pH (5.4) compared to 64 % at physiological pH (7.4) over a 96-h duration. In vitro cytotoxicity experiments validated precise targeting, leading to a 40 % decrease in HepG2 cell viability and a 94 % preservation of L929 normal cell viability. Alongside these findings, machine learning modeling techniques (Gradient Boosting, Neural Networks, Random Forest, and SVM) were devised to replicate release kinetics, accurately characterizing non-linear pH–time profiles with remarkable precision (R² &gt; 0.97). These prediction methodologies provide computational assistance for enhancing nanocarrier design beyond existing kinetic models. This multi-functional platform effectively mitigates some of the major limitations of conventional QC treatment, including low solubility, systemic toxicity, and non-specific biodistribution, and thereby offers a biocompatible and computationally optimized platform for precision oncology.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107555"},"PeriodicalIF":4.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154565","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}