Journal of Drug Delivery Science and Technology最新文献

{"title":"An effective approach in osteoarthritis: Diacerein-loaded solid lipid nanoparticles, preparation and evaluation for targeted therapy","authors":"Badarqa Tul Ayesha ,&nbsp;Alia Erum ,&nbsp;Nariman Shahid ,&nbsp;Ume Ruqia Tulain ,&nbsp;Uzma Saleem","doi":"10.1016/j.jddst.2025.106856","DOIUrl":"10.1016/j.jddst.2025.106856","url":null,"abstract":"<div><div>Diacerein (DC) is primarily used for the treatment of degenerative diseases, such as osteoarthritis (OA). The purpose of this study is to develop a stable targeted preparation of DC for intra-articular delivery with prolonged effect. The Response Surface methodology approach was applied to optimize DC-loaded solid lipid nanoparticles (DC-SLNs). For optimization of SLNs, the DC-SLNs were fabricated with different ratios of stearic acid and glyceryl monostearate. SLNs of DC were prepared by a hot homogenization process and were characterized for particle size, zeta potential, polydispersity index, entrapment efficiency, and drug loading. FTIR, DSC, PXRD, and SEM analysis were also performed. <em>In-vitro</em> dissolution studies were also performed for 24 h. <em>In-vivo</em> studies were executed by utilizing papain-induced osteoarthritis rat model including plain DC and DC-SLNs administered orally and intra-articularly. The knee diameter was measured and behavioral studies were done which include the gait analysis, locomotor activity, and forced swim test. The results of these studies revealed that DC-SLNs administered intra-articularly have anti-inflammatory effects in the osteoarthritic rat model. Biochemical analysis displayed a positive effect on the osteoarthritic animal model. The inflammatory marker mediators like; TNF-α, IL-6, and NF-κB, were evaluated and indicated that intra-articular administration of DC-SLNs IA inhibited the inflammation and was also found effective in protecting against cartilage degradation. Thus, the study concluded that DC-SLNs IA can be used as an efficient anti-inflammatory delivery system with minimal side effects.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"108 ","pages":"Article 106856"},"PeriodicalIF":4.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791682","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 β-carotene-loaded casein nanoparticles with enhanced stability, permeability, and antioxidant activity that mitigates dexamethasone-induced muscle atrophy","authors":"Wan-Yi Liu ,&nbsp;Yung-Yi Cheng ,&nbsp;Yih-Fung Chen ,&nbsp;Yu-Tse Wu","doi":"10.1016/j.jddst.2025.106865","DOIUrl":"10.1016/j.jddst.2025.106865","url":null,"abstract":"<div><div>β-carotene (BC)-loaded casein nanoparticles (BC-CNPs) were developed to enhance the oral absorption and intestinal permeability of β-carotene and evaluated their antioxidant activity in the present study. The nanoparticles were fabricated using a simple coacervation method, which yielded particles with an average size of 217.4 nm, polydispersity index of 0.149, zeta potential of −18.49 mV, and encapsulation efficiency of 88 %, indicating uniformity and stability. Physicochemical evaluation revealed that the BC-CNPs were spherical with β-carotene in an amorphous form. The stability of BC-CNPs under heat and lyophilization was also confirmed, and they exhibited 1.6-fold enhancement in the permeability assay compared with BC, indicating an improvement in oral absorption. <em>In vitro</em> antioxidant tests demonstrated improved 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid free radical scavenging ability and ferric reducing antioxidant power. Fluorescence assay confirmed that the k_q value of the BC-CNPs was higher than the maximum scatter collision quenching value, revealing the formation of a ground-state acceptor–ligand complex. Molecular docking results revealed that BC and sodium caseinate are combined via van der Waals and hydrophobic interactions. Furthermore, <em>in vivo</em> studies using a mouse model showed that BC-CNPs could prevent dexamethasone-induced muscle atrophy, increase glutathione peroxidase and catalase levels by 1370.0 % and 11.8 %, respectively, and reduce malondialdehyde levels and advanced oxidation protein products by 27.0 % and 30.1 %, respectively, in the plasma. These findings suggest that casein nanoparticles can effectively enhance BC oral absorption and mitigate muscle atrophy and oxidative stress. Overall, BC-CNPs can improve muscle atrophy by reducing oxidative stress.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"107 ","pages":"Article 106865"},"PeriodicalIF":4.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768647","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":"Film-forming solutions for cutaneous application: current challenges and future directions in formulation design and characterization framework","authors":"Sandra Milinković ,&nbsp;Ljiljana Đekić","doi":"10.1016/j.jddst.2025.106863","DOIUrl":"10.1016/j.jddst.2025.106863","url":null,"abstract":"<div><div>Film-forming solution (FFS) implies a novel formulation strategy for liquid preparations for cutaneous application with numerous advantages in comparison with compendial dosage forms, including flexibility of composition (active pharmaceutical ingredient (API) solution in volatile and non-volatile solvents, with film-forming polymers, plasticizers and chemical permeation agents) and the method of administration (rubbing or spraying). Research over the past two decades indicates the potential of FFS for comparable or improved dermal, regional and transdermal delivery of small-molecule drugs due to improved passive diffusion through: volatile solvents evaporation and API (super)saturation, and potential increase in stratum corneum (SC) permeability caused by excipients. Current commercial exploitation of FFS is limited due to demanding pharmaceutical development, the backbone of which is formulation design and product characterization. This comprehensive review gives insight into the complex relationship between the formulation composition, quality attributes (physicochemical properties, microstructure) and <em>in vitro</em> performance (drug release and permeation) of FFS. A characterization framework is proposed, taking into account published studies, relevant pharmacopoeial standards and announced guidelines of the European Medicines Agency (EMA) and The United States Food and Drug Administration (FDA). The importance of specific tests for evaluating the transformation of FFS at the site of application and the quality attributes of the <em>in situ</em> formed film, was pointed out. Directions for pharmaceutical development improvement are given, including the favoring of environmentally acceptable and biocompatible excipients, introduction of <em>in silico</em> formulation optimization techniques and development of standardized methodology for reliable and comparable assessment of quality, efficiency and safety of FFS.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"108 ","pages":"Article 106863"},"PeriodicalIF":4.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768497","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":"Curcumin loaded hyaluronan modified niosomes: Preparation, characterization and anti-cancer activity on triple-negative breast cancer cells","authors":"Mozhgan Abasi ,&nbsp;Zaynab Sadeghi Ghadi ,&nbsp;Younes Pilehvar ,&nbsp;Pedram Ebrahimnejad","doi":"10.1016/j.jddst.2025.106869","DOIUrl":"10.1016/j.jddst.2025.106869","url":null,"abstract":"<div><div>Curcumin is a herbal polyphenolic compound with anti-cancer properties, but its low solubility, stability and bioavailability limit its therapeutic potential. In this study, we developed niosomes, nanosized vesicles composed of tween 80, Sorbitan monostearate, cholesterol and hyaluronan, as a novel delivery system for curcumin. The curcumin-loaded hyaluronan modified niosomes (cur-nio) were prepared by thin-film hydration method and characterized for their morphology, zeta potential, particle size and <em>in vitro</em> drug release. The anti-cancer activity and apoptotic effect of cur-nio were evaluated on MDA-MB-231 cell line by MTT assay, Real time PCR and Annexin V-FITC/PI staining. Moreover, migration and invasion phenotypes of cells were determined by transwell assays and wound healing assays. We were also interested in determining cur-nio effects on tumorigenicity of MDA-MB-231 cells by mammosphere formation assay. The results showed that the cur-nio had a spherical shape, a negative charge, a mean diameter of about 251 ± 7.14 nm and a high encapsulation efficiency of about 97.96 ± 0.55. The cur-nio exhibited a sustained release profile of curcumin. The cur-nio showed significant inhibition of cell viability and induction the expression of essential apoptotic genes compared to free curcumin and blank niosomes. The IC50 value of cur-nio was about 30 μM, which was approximately 2 times lower than that of free curcumin. Also, our results showed that cur-nio significantly inhibits cell migration, invasion, mammosphere formation and proliferation rate <em>in vitro</em>.These findings suggest that niosomes are a promising carrier for enhancing the delivery and efficacy of curcumin in cancer therapy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"108 ","pages":"Article 106869"},"PeriodicalIF":4.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760234","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":"Modulating drug delivery with nano-selenium capped chitosan reverse micelles for anticancer potential","authors":"Radha Gosala ,&nbsp;Raghunandhakumar Subramanian ,&nbsp;Balakumar Subramanian","doi":"10.1016/j.jddst.2025.106860","DOIUrl":"10.1016/j.jddst.2025.106860","url":null,"abstract":"<div><div>Combining nanoparticles with biopolymer protective coatings offer an appealing cancer treatment strategy. This study develops chitosan (CS) coated selenium (Se) nanocarriers <em>via</em> reverse micellar method using surfactants such as sodium bis(2-ethylhexyl)sulfosuccinate (AOT) and N-cetyl-N,N,N-trimethylammonium bromide (CTAB) to enhance the sustained release of daunorubicin (DNR) and to improve the stability of drug carriers. The chemically reduced Se nanoparticles aggregated into elongated rod shapes, approximately 60 nm in diameter, and were coated with CS to form a protective layer that sustained the drug release. Zeta potential measurements revealed that CS coating increased the surface charge of Se nanoparticles, with values of 33 ± 6.1 mV for CTAB system and 30 ± 5.7 mV for AOT systems. Additionally, AOT resulted in higher encapsulation efficiency (70 %) compared to CTAB (62 %). DNR drug release at pH 5.4 showed a significantly higher cumulative release (88 %) compared to pH 7.4 (75 %), demonstrating pH-dependent release behavior. The CS coating acts as a gatekeeper, regulating the release of DNR from Se nanoparticles. <em>In vitro</em> studies showed that both CS-CTAB-Se@DNR and CS-AOT-Se@DNR carriers exhibited higher cytotoxicity and increased ROS generation compared to bare Se nanoparticles. These findings highlight the potential of CS-Se@DNR nanocarriers as an effective strategy for cancer treatment.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"108 ","pages":"Article 106860"},"PeriodicalIF":4.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783857","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":"Eco-friendly synthesis and multifunctional evaluation of silver nanoparticles using Boleophthalmus dussumieri mucus: Antibacterial, anticancer, and predictive modeling applications","authors":"Fahimeh Saberi ,&nbsp;Ahmad Gharzi ,&nbsp;Ashraf Jazayeri ,&nbsp;Vahid Akmali ,&nbsp;Khosrow Chehri ,&nbsp;Naser Karimi ,&nbsp;Nasrin Babajani ,&nbsp;Muhammad Rizwan ,&nbsp;Elahe Baratalipour","doi":"10.1016/j.jddst.2025.106843","DOIUrl":"10.1016/j.jddst.2025.106843","url":null,"abstract":"<div><div>The synthesis of eco-friendly silver nanoparticles has attracted significant attention from researchers, primarily due to their wide-ranging applications in contemporary medicine, having antioxidant, antimicrobial, and anticancer properties. In this study, green-synthesized AgNPs (MM-Ag NPs) using <em>Boleophthalmus dussumieri</em> mucus were prepared and characterized for their antibacterial, antibiofilm, antihemolytic, and anticancer properties. Characterization techniques UV–vis, SEM, TEM, and AFM confirmed that the nanoparticles were uniformly spherical, ranging from 10 to 30 nm. The nanoparticles showed a UV–visible absorption peak at 428 nm, indicating a successful reduction of AgNO₃. FTIR analysis revealed bioactive molecules on their surfaces, while X-ray diffraction indicated a face-centered cubic structure, with a zeta potential of −16 ± 0.65 mV. MM-Ag NPs exhibited strong antibacterial activity against the confirmed bacterial strains, including <em>Escherichia coli</em>, <em>Pseudomonas aeruginosa</em>, and <em>Staphylococcus aureus</em>, with a notable 22 mm inhibition zone against <em>E. coli</em>. In cytotoxicity assays on MCF-7 cancer cells, an IC50 value of 48.73 % was recorded at 256 ppm, highlighting their anticancer potential. Biocompatibility tests demonstrated safety through membrane stabilization assays using red blood cells. Machine learning techniques were also applied to predict values related to <em>Citrobacter freundii</em> and <em>Morganella morganii</em> for MM-Ag NPs. The best model for predicting their concentrations was identified, showcasing the effectiveness of ML in enhancing research efficiency and reducing trial-and-error approaches. In conclusion, this study underscores the significant biological potential of AgNPs derived from <em>B. dussumieri</em> mucus as promising antimicrobial agents against bacterial infections; potential anticancer agents in cancer therapy, and eco-friendly candidates for drug delivery systems.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"108 ","pages":"Article 106843"},"PeriodicalIF":4.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746823","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":"Intranasal Apocynin-loaded nanostructured lipid carriers (NLCs) for Alzheimer's disease therapy: Formulation, optimization, and pharmacokinetic evaluations","authors":"Supriya Samala,&nbsp;Akshada Mhaske,&nbsp;Rahul Shukla","doi":"10.1016/j.jddst.2025.106862","DOIUrl":"10.1016/j.jddst.2025.106862","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by cognitive impairment and neuronal degeneration. Delivering drugs to the brain remains a challenge due to the restrictive nature of the blood-brain barrier (BBB). Intranasal (IN) administration offers a promising alternative by utilizing the olfactory and trigeminal pathways to bypass the BBB. Apocynin (APO), a natural antioxidant, has been explored for its potential in reducing oxidative stress linked to AD. This study aimed to develop APO-loaded nanostructured lipid carriers (APO-NLCs) and evaluate their physicochemical properties, drug release profile, cellular uptake, and brain distribution following intranasal and oral administration.</div></div><div><h3>Methods</h3><div>APO-NLCs were formulated using a melt emulsification method and optimized via a Box-Behnken design. The nanoparticles were characterized for size, surface charge, entrapment efficiency, and drug loading. Morphological analysis, <em>in vitro</em> drug release, <em>ex vivo</em> nasal permeation using goat nasal mucosa, and cellular uptake studies in SH-SY5Y cells were conducted. Pharmacokinetic and biodistribution studies compared drug accumulation in the brain following intranasal and oral administration.</div></div><div><h3>Results</h3><div>The optimized APO-NLCs had a particle size of 138.8 nm, a zeta potential of −8.65 mV, an entrapment efficiency of 60.21 %, and a drug loading of 7.58 %. The formulation showed a biphasic release pattern, with 45.80 % of the drug released over 24 h, following Higuchi kinetics. Intranasal administration led to significantly higher brain drug accumulation compared to oral delivery, indicating improved bioavailability and CNS targeting.</div></div><div><h3>Conclusion</h3><div>APO-NLCs demonstrated effective drug delivery to the brain, with intranasal administration offering superior bioavailability over oral administration. These findings highlight their potential for treating AD and warrant further investigation.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"108 ","pages":"Article 106862"},"PeriodicalIF":4.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760331","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 zein-gum Arabic nanoparticles for astaxanthin encapsulation and topical delivery: Preparation and characterization","authors":"Wenpeng Song ,&nbsp;Wei Wei ,&nbsp;Biao Zhou ,&nbsp;Ning Lv ,&nbsp;Heng Qin ,&nbsp;Fei Huan ,&nbsp;Xiaoling Zhang","doi":"10.1016/j.jddst.2025.106858","DOIUrl":"10.1016/j.jddst.2025.106858","url":null,"abstract":"<div><div>Astaxanthin (AST), a potent antioxidant, holds great promise for skin health and cosmetic applications but is limited by poor water solubility and stability. This study presents the development of zein nanoparticles modified with gum arabic (GA) for the encapsulation of AST, serving as a topical nanocarrier for AST to enhance its dermal bioavailability and topical delivery. The optimized zein-GA-AST nanoparticles (Z-GA-AST) exhibited a spherical nanostructure with a mean particle size of 199.03 ± 4.63 nm (PDI &lt;0.2) and achieved a high encapsulation efficiency of 90.34 ± 1.74 %. FT-IR spectroscopy analysis confirmed the successful encapsulation of AST within the nanoparticles. The AST-loaded nanoparticles exhibited significantly superior antioxidant activity compared to free AST. At an equivalent astaxanthin concentration of 10 μg/mL, the ABTS and DPPH radical scavenging efficiencies of the nanoparticles were at least 153 % and 128 % higher than those of free AST, respectively. The incorporation of GA enhanced the physicochemical stability and astaxanthin retention of the nanoparticles under various conditions, including different salt ion concentrations, temperatures, and storage durations, by facilitating the formation of a more compact nanostructure. The skin permeation behavior of the nanoparticles was evaluated using Franz diffusion cells and porcine skin. The results demonstrated that Z-GA2-AST1 exhibited significantly higher skin retention (48.37 %) and lower astaxanthin permeation (10.20 %) compared to free astaxanthin. This study provides valuable insights into the preparation and characterization of biocompatible nanoparticles for AST encapsulation, could become a potential formulation for topical delivery applications in cosmetics and topical drug delivery systems.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"107 ","pages":"Article 106858"},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747295","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":"Drug-drug solid dispersions of two hydrophobic antipsychotics and DP-VPA-C18 with improved pharmacodynamic and pharmacokinetic profiles","authors":"Chao Hao ,&nbsp;Wenwen Liu ,&nbsp;Chenxin Duan ,&nbsp;Zhiling Chen ,&nbsp;Jinmeng Han ,&nbsp;Jie Song ,&nbsp;Tao Zhuang ,&nbsp;Xiaohua Zhang","doi":"10.1016/j.jddst.2025.106859","DOIUrl":"10.1016/j.jddst.2025.106859","url":null,"abstract":"<div><div>DP-VPA is a phospholipid prodrug of valproic acid which has been highly recommended as an adjunct to antipsychotics for the treatment of schizophrenia, and phospholipids are considered as promising excipients in solid dispersions (SDs). This study aimed to explore the effect of SDs of two poorly water-soluble antipsychotics (Aripiprazole, ARI; ziprasidone hydrochloride, ZIP·HCl) with DP-VPA on their pharmacodynamic and pharmacokinetic profiles. The SDs of ARI or ZIP·HCl containing DP-VPA-C₁₈ (DV₁₈) were prepared by the solvent evaporation methods and characterized by powder X-ray diffraction, differential scanning calorimetry and infrared spectroscopy. The apparent solubility of ARI or ZIP·HCl in the prepared SDs was improved at least 2-fold than pure drugs in four different media. Those SDs also exhibited synergistic antipsychotic effects in reversing apomorphine-induced climbing behavior in mice. Furthermore, the optimal drug ratios between ARI or ZIP·HCl and DV₁₈ were determined as 1:10 (SD-ARI 10) and 1:8 (SD-ZIP 8) respectively, and SD-ARI 10 and SD-ZIP 8 showed good physical stability under long-term storage conditions. The oral bioavailability of SD-ZIP 8 was improved 1.67 times in rats when compared to the pure drug. This study highlighted the potential of DP-VPA as a promising carrier drug for antipsychotics in SDs to improve their pharmacokinetic and pharmacodynamic profiles.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"108 ","pages":"Article 106859"},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768499","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":"Cyclodextrin-based chemically modified pH-Responsive new kind of aldehyde-functionalized nanosponge nanoparticles for doxorubicin hydrochloride delivery","authors":"Ayhan Bergal ,&nbsp;Muberra Andac ,&nbsp;Francesco Trotta","doi":"10.1016/j.jddst.2025.106853","DOIUrl":"10.1016/j.jddst.2025.106853","url":null,"abstract":"<div><div>This study aimed to develop and assess ALD-NS nanoparticles (NPs) as pH-responsive drug delivery systems. Functionalized β-cyclodextrin derivatives (OX-β-CDs) containing aldehyde (CHO) groups were synthesized and crosslinked with pyromellitic dianhydride (PMDA) to form water-soluble ALD-NS-NPs. Doxorubicin hydrochloride (DOX·HCl), containing an NH₂ side group, was incorporated bidirectionally into ALD-NS through the reflux method, forming pH-sensitive Schiff base (C=N) bonds and integrating into the hydrophilic portion of ALD-NS. Characterization of the ALD-NS + DOX complex confirmed successful drug loading, with a particle size of 372.7 ± 8.21 nm, a negative zeta potential of −12.8 ± 1.54 mV, and a high encapsulation efficiency of 85.5 %. In vitro drug release studies conducted under three distinct buffer conditions revealed a higher release rate at pH 5.2 compared to pH 7.4, which was attributed to the hydrolysis of Schiff base bonds and crosslinker in the acidic environment. Cytotoxicity and cellular uptake assays performed on A549 cancer cells demonstrated dose- and time-dependent responses. ALD-NS + DOX displaying higher cell viability and increased drug accumulation within cells when compared to free DOX at equivalent concentrations. Drug release kinetics, assessed using the Korsmeyer-Peppas model (R² = 0.97), revealed a release mechanism that involves both dissolution (hydrolysis) and non-Fickian diffusion, with diffusion coefficients of 0.622 in PBS and 0.71 in NaOAc at pH 5.2. These findings suggest that the ALD-NS-NP system is a promising candidate for targeted drug delivery, particularly for drugs with NH₂ functional groups in acidic environments.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"107 ","pages":"Article 106853"},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747411","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}