Ghulam Muhayyudin Chattha , Muhammad Awais Chattha , Walter Orlando Beys-da-Silva , Lucélia Santi
{"title":"Nanoparticle-mediated photothermal therapy and photodynamic therapy: A novel strategy for antifungal drug delivery and treatment","authors":"Ghulam Muhayyudin Chattha , Muhammad Awais Chattha , Walter Orlando Beys-da-Silva , Lucélia Santi","doi":"10.1016/j.jddst.2025.107125","DOIUrl":"10.1016/j.jddst.2025.107125","url":null,"abstract":"<div><div>Fungal infections represent considerable global health risks, especially in immunocompromised populations. Despite advances in antifungal medications, existing therapies are limited by toxicity, inadequate absorption, and the rise of drug-resistant fungus species. In this review, we explore the novel uses of photodynamic therapy (PDT) and nanoparticle-mediated photothermal therapy (PTT) as cutting-edge approaches to improving the effectiveness and delivery of antifungal medications. In addition to addressing the difficulties presented by treatment-resistant fungal diseases, the study emphasizes the potential of nanomaterials to enhance drug solubility, targeting, and controlled release. Using nanomaterials such as gold, silver, and carbon-based nanoparticles has demonstrated encouraging results in improving therapy outcomes against pathogenic fungi such as <em>Candida albicans</em> and <em>Aspergillus fumigatus.</em> Furthermore, the combination of PTT and PDT, together with standard antifungal drugs, may overcome ways to resist by damaging fungal cell structures via localized heat and reactive oxygen species production. The analysis finds that nanotechnology-based techniques have significant potential for overcoming the limits of traditional antifungal medicines and improving clinical outcomes for fungal infections.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107125"},"PeriodicalIF":4.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253596","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":"Enhancing luteolin solubility through solid dispersion-based oral gels: A novel approach for periodontal disease treatment","authors":"Maria Koromili , Afroditi Kapourani , Konstantina Chaclioutaki , Nikoletta Christoudia , Spyros Pettas , Dimitra Dafou , Theodoros Sklaviadis , Dimitrios A. Andreadis , Spyros Papageorgiou , Andreana N. Assimopoulou , Konstantinos Xanthopoulos , Dimitrios N. Fatouros , Panagiotis Barmpalexis","doi":"10.1016/j.jddst.2025.107121","DOIUrl":"10.1016/j.jddst.2025.107121","url":null,"abstract":"<div><div>Luteolin (LUT) is a bioactive flavonoid with numerous pharmacological properties, such as antioxidant, antimicrobial, and anti-cancer activity. A prominent example of LUT's properties concerns its administration for the treatment of periodontal disease. However, its low water solubility poses a serious challenge regarding its formulation into an effective dosage form. To this end, the present study investigates the incorporation of LUT's solid dispersions (SDs) into oral gels, as a way to improve LUT solubility in saliva for the treatment of periodontitis. Initially, SDs of LUT were formulated at drug-to-polymer weight ratios of 1:9 and 1:12 using either polyethylene glycol 6000 (PEG) or poloxamer P188 (P188), employing both melting and solvent evaporation techniques. Subsequently, these drug-loaded SDs were integrated into oral gels designed for the local treatment of periodontal disease within the mouth. The SDs resulted in a remarkable solubility enhancement for LUT, showing up to a 16-fold increase compared to its pure crystalline form. Physicochemical characterization using differential scanning calorimetry (DSC) and powder X-ray diffractometry (pXRD), revealed that LUT was amorphously dispersed within the SDs, while ATR-FTIR spectroscopy indicated the presence of significant molecular interactions between the drug and the matrix/carriers. The gels containing the SDs of LUT displayed appropriate rheological properties for handling and storage, while the <em>in vitro</em> dissolution studies in simulated saliva revealed that the PEG SD-based oral gels were able to significantly enhance LUT's release. Moreover, cell viability studies, which examined two promising SDs (one with PEG and one with P188), revealed negligible cytotoxicity, suggesting that the prepared formulations exhibit favorable and non-toxic characteristics. In addition, <em>in vitro</em> assays demonstrated that the formulations retained LUT's anti-inflammatory effect. Finally, <em>ex vivo</em> permeation studies using porcine buccal tissue demonstrated that P188-based SD, incorporated into a placebo gel, enhanced the ability of LUT to partition into and accumulate within the mucosal tissue, resulting in more than three-times the accumulation compared to the gel containing the neat drug. Therefore, the preparation of SD oral gels for LUT can be regarded as a prospective technique with strong potential for the improvement of the API's solubility and hence, its administration in the oral cavity for the topical treatment against periodontitis.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107121"},"PeriodicalIF":4.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204680","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}
Sara S. Abdel-Hakeem , Mahmoud Abdel-Zaher Abdel-Samiee , Mona Mohamed Ali Khalaf , Gamal Hassan Abed
{"title":"Impact of quercetin conjugated silver nanoparticles on neuroinflammation, endothelial permeability, and pharmacokinetics in vivo against genotype T4, Acanthamoeba polyphaga","authors":"Sara S. Abdel-Hakeem , Mahmoud Abdel-Zaher Abdel-Samiee , Mona Mohamed Ali Khalaf , Gamal Hassan Abed","doi":"10.1016/j.jddst.2025.107116","DOIUrl":"10.1016/j.jddst.2025.107116","url":null,"abstract":"<div><div><em>Acanthamoeba</em> spp., pose a growing global health concern due to their association with granulomatous amoebic encephalitis (GAE), particularly in immunocompromised individuals. Treatment options remain limited and often ineffective due to drug resistance, delayed diagnosis, and the parasite's ability to induce neuroinflammation and disrupt the blood-brain barrier (BBB). Therefore, this study investigates, for the first time, the therapeutic role of quercetin-conjugated silver nanoparticles (Q-AgNPs) in modulating neuroinflammatory responses, enhancing endothelial barrier integrity, and improving pharmacokinetic properties of this nanoformulation in an experimental model. A total of 105 male mice were divided into seven groups, representing both immunocompetent and immunosuppressed animals, with appropriate control groups. Q-AgNPs were synthesized and characterized using spectrophotometer, transmission electron microscope, zeta-potential, loading efficiency, <em>invitro</em> release analysis, and FTIR analysis. Hematological indices showed improvement over time with treatment, with significant increases in erythrocytes, hemoglobin, and hematocrit levels, alongside gradual reduction in humoral inflammatory reaction. Additionally, Q-AgNPs treatment reduced proinflammatory cytokines (TNF-α and IL-1β) and BBB permeability marker (MMP9), while significantly increasing anti-inflammatory cytokine (IL-10). Histopathological examinations showed that Q-AgNPs alleviated neural lesions and glial cell reaction. Immunohistochemical analysis highlighted the role of Q-AgNPs in reducing the trans-endothelial immune cell migration and in delaying GAE-induced brain atrophy through decreased PECAM-1 gene expression in the brain regions. Molecular docking revealed that Q-AgNPs had a strong binding affinity with the mitochondrial respiratory protein NAD2, offering enhanced pharmacokinetic properties compared to quercetin alone. This study support Q-AgNPs as a promising therapeutic strategy to combat <em>A. polyphaga</em>-induced GAE by modulating neuroinflammation pathways and improving drug delivery.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107116"},"PeriodicalIF":4.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221017","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}
Fatemeh Karimzadeh , Karim Mahnam , Mehdi Rezaee , Fatemeh Toghroli , Rahim Malekzadeh , Fatemeh Elahian , Seyed Abbas Mirzaei
{"title":"Design, synthesis, and evaluation of cell-penetrating anticancer peptides to enhance the antitumor activity of liposomal daunorubicin: A molecular dynamics and experimental study","authors":"Fatemeh Karimzadeh , Karim Mahnam , Mehdi Rezaee , Fatemeh Toghroli , Rahim Malekzadeh , Fatemeh Elahian , Seyed Abbas Mirzaei","doi":"10.1016/j.jddst.2025.107115","DOIUrl":"10.1016/j.jddst.2025.107115","url":null,"abstract":"<div><div>Targeted delivery and effective penetration into cancer cells are key factors in the success of drug delivery systems. This study aimed to design, synthesize, and evaluate cell-penetrating anticancer peptides (ACPs), and to develop functionalized nanoliposomes with ACPs and an antibody to enhance the specificity and cellular uptake of liposomal daunorubicin (daunosome) in multidrug-resistance cancer cells. Here, a library of 1290 peptides was screened for anticancer potential and physicochemical properties, and the top candidates were evaluated for permeability to cell membrane models using molecular dynamics simulations. The selected peptides (Pep5 and Pep6) were synthesized, used to modify daunosomes, and evaluated for cytotoxicity, apoptosis, drug accumulation, and efflux kinetics in HDF, EPG85.257, and EPG85.257RDB cell lines. The liposomal formulations were characterized using FTIR, TEM, X-ray diffraction, and DLS analysis. The potential of mean force (PMF) profiles predicted that Pep6 required less energy than Pep5 to cross the membrane of cancer cells. The cytotoxicity assay showed that the peptides selectively reduced the viability of the cancer cell lines (EPG85.257RDB and EPG85.257) more than that of normal HDF cells. The daunorubicin encapsulation rate and average diameter of the daunosome formulations were approximately 93 % and 264–314 nm, respectively. The highest apoptosis rates were observed in the EPG85.257 cell line following treatment with Ab<sup>+</sup>TAT<sup>+</sup>daunosome (44.4 %) and in EPG85.257RDB cells treated with Ab<sup>+</sup>Pep6<sup>+</sup>daunosome (29.3 %). Drug accumulation was significantly increased following the decoration of daunosomes with trastuzumab, TAT, Pep5, and Pep6. The results indicate that the designed ACPs, in combination with the trastuzumab, can enhance the antitumor activity of liposomal daunorubicin.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107115"},"PeriodicalIF":4.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194829","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":"Self-oxygenating GMZ@HA nanocarriers enhance doxorubicin cytotoxicity in hypoxic breast cancer","authors":"Farideh Khoshsokhan , Azadeh Meshkini","doi":"10.1016/j.jddst.2025.107117","DOIUrl":"10.1016/j.jddst.2025.107117","url":null,"abstract":"<div><div>Tumor hypoxia has been recognized as a significant challenge in cancer therapy, with certain chemotherapeutic agents such as doxorubicin (DOX) exhibiting reduced efficacy under low oxygen conditions. In the present study, a multifunctional nanocomposite (GMZ@HA-DOX) was developed to alleviate tumor hypoxia and enhance DOX efficacy in breast cancer treatment. Graphene oxide (GO) nanosheets were functionalized with manganese dioxide (MnO<sub>2</sub>) nanoparticles and hyaluronic acid-coated zinc peroxide (ZnO<sub>2</sub>@HA), onto which DOX was subsequently loaded. Under the acidic conditions characteristic of the tumor microenvironment, ZnO<sub>2</sub>@HA generated hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), which was catalytically converted into oxygen by MnO<sub>2</sub>, thereby increasing local oxygen levels. Uniform dispersion of MnO<sub>2</sub> (approximately 10 nm) and ZnO<sub>2</sub> (approximately 20 nm) on the GO matrix was confirmed by electron microscopy and energy-dispersive X-ray analysis, with a DOX loading efficiency of approximately 50 %. The nanocomposite exhibited sustained, pH-dependent drug release, with higher DOX release at pH 5.4 than at pH 7.4 over 72 h, supporting tumor-specific delivery. The oxygen-generating capability of the nanocomposite was assessed using an oxygen probe assay, which revealed a 2.7- to 3-fold increase in oxygen production compared to control conditions. <em>In vitro</em> experiments using MCF-7 breast cancer cells under normoxic and hypoxic conditions demonstrated that treatment with the nanocomposite reduced cell viability, lowered IC<sub>50</sub> value of DOX, and enhanced intracellular drug accumulation. Enhanced reactive oxygen species production, increased apoptosis, and inhibited cell migration were also observed, while minimal toxicity was detected in HEK-293 renal cells. Furthermore, in an <em>ex vivo</em> multicellular model simulating <em>in vivo</em> tumor tissue, the nanocomposite was shown to penetrate deeply and effectively destroy tumor cells. These findings indicate that the oxygen-generating nanocomposite overcomes hypoxia-induced drug resistance and significantly improves the targeted delivery and therapeutic efficacy of DOX, representing a promising strategy for treating hypoxic tumors.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107117"},"PeriodicalIF":4.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178774","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":"Natural catechin containing α-Lactalbumin based electrospun nanofibers for arthritis treatment and bone repair","authors":"Zhelong Zhang , Beini Cen , Junjie Xia , Hai Huang , Yichen Meng","doi":"10.1016/j.jddst.2025.107060","DOIUrl":"10.1016/j.jddst.2025.107060","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and bone erosion that pose significant challenges in orthopedics, necessitating innovative therapeutic approaches. Current treatments often have limited efficacy and significant side effects. Here, we report the development of α-lactalbumin-based curcumin-reinforced injectable electrospun nanofibers containing epigallocatechin gallate (EGCG) (EC/αL-NFs) for RA treatment and bone repair. The nanofibers exhibited excellent biocompatibility, biodegradability, and mechanical properties. Curcumin and EGCG incorporation significantly enhanced anti-inflammatory and antioxidant activities. <em>In vitro</em> and <em>in vivo</em> studies demonstrated the nanofibers' potential for RA treatment, reducing inflammation and promoting bone repair. The X-ray evaluations and immunohistochemical analysis revealed excellent treatment efficiency of the EC/αL-NFs for arthritis and bone chondrogenesis. The EC/αL-NFs also promoted osteogenic differentiation and bone matrix deposition. This study provides a promising approach for the development of injectable nanofibers for arthritis treatment and bone tissue engineering applications.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107060"},"PeriodicalIF":4.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189997","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}
Giuseppe Francesco Racaniello , Monica Pistone , Annalisa Cutrignelli , Corrado Cuocci , Rosanna Rizzi , Nunzio Denora , Antonio Lopalco , Angela Assunta Lopedota
{"title":"Solid-state characterization and solubility enhancement strategies for Olaparib in formulation development","authors":"Giuseppe Francesco Racaniello , Monica Pistone , Annalisa Cutrignelli , Corrado Cuocci , Rosanna Rizzi , Nunzio Denora , Antonio Lopalco , Angela Assunta Lopedota","doi":"10.1016/j.jddst.2025.107123","DOIUrl":"10.1016/j.jddst.2025.107123","url":null,"abstract":"<div><div>During the formulation development of anticancer drug Olaparib (OLA), we observed that two batches (Batch 1 and Batch 2) obtained from the same supplier exhibited different solubility and dissolution behavior despite their identical chemical purity (99.9 %).</div><div>A comprehensive solid-state characterization was conducted. The Differential Scanning Calorimetry analysis showed distinct thermal behavior, with endothermic peaks at 202 and 215 °C, attributed to two polymorphic forms, as confirmed by Fourier Transform Infrared Spectroscopy and Thermogravimetric Analysis. Powder X-ray Diffraction analysis revealed that Batch 1 contained a mixture of OLA Form A (major) and Form L (minor, <em>∼</em>15 % w/w), and exhibited lower crystallinity compared to Batch 2. Batch 2 consisted exclusively of pure OLA Form L, whose crystal structure was reported here for the first time. Morphology analysis indicated that Batch 1 presented particles with heterogeneous dimensions (2–60 μm), while Batch 2 showed a homogeneous size distribution (∼5 μm), resulting in differences in density and specific surface area. These differences in solid-state properties further contributed to observed variations in equilibrium solubility and intrinsic dissolution rate (IDR), with Batch 1 exhibiting a higher solubility and IDR (0.1239 mg/mL; 26.74 mg/cm<sup>2</sup>·min<sup>−1</sup>) than Batch 2 (0.0609 mg/mL; 13.13 mg/cm<sup>2</sup>·min<sup>−1</sup>) at 37 °C.</div><div>The addition of Soluplus® and hydroxypropyl-β-cyclodextrin significantly enhanced OLA solubility in concentration-dependent manner, up to 1.2-fold and 12-fold for Batch 1 and 2.5-fold and 26-fold for Batch 2, respectively, after 72 h of incubation. These findings demonstrate that, despite initial differences in polymorphic composition and particle morphology, appropriate solubilizing agents can mitigate batch-to-batch variability and optimize OLA solubility.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107123"},"PeriodicalIF":4.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184552","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 supramolecular dissolving microneedles for enhanced transdermal delivery of azelaic acid in acne vulgaris treatment","authors":"Yuxu Chen, Yuanyu Xu, Jingqing Zhang, Xinjun Xu","doi":"10.1016/j.jddst.2025.107108","DOIUrl":"10.1016/j.jddst.2025.107108","url":null,"abstract":"<div><div>Acne vulgaris is a common skin condition affecting individuals of various age groups, significantly impacting their quality of life. Although azelaic acid (AZA) is widely used in acne treatment due to its anti-inflammatory, antibacterial, and tyrosinase inhibitory properties, its low aqueous solubility limits its transdermal absorption and reduces therapeutic efficacy. Dissolving microneedles (DMNs), fabricated from water-soluble materials, have shown great potential as a strategy for improving transdermal drug delivery. However, DMNs face challenges in encapsulating poorly soluble drugs like AZA. In this study, we developed cyclodextrin-based supramolecular DMNs loaded with AZA, in which the microneedles are composed entirely of inclusion complexes to enhance the transdermal delivery efficiency of AZA for treating acne. AZA was encapsulated into hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) using a solvent evaporation technique, resulting in respective 34.9-fold and 25.4-fold increases in AZA solubility. The inclusion complexes demonstrated superior antibacterial activity in inhibition zone assays and enhanced tyrosinase inhibitory activity compared to free AZA in aqueous solution, suggesting enhanced dispersion and biological activity. The DMNs exhibited excellent mechanical strength and maintained a high drug-loading capacity of AZA, facilitating efficient penetration through the stratum corneum. <em>In vitro</em> permeation test showed 24-h percutaneous permeability rates at 68.69 ± 3.79 % and 73.59 ± 4.23 % for AZA/HP-β-CD DMNs and AZA/SBE-β-CD DMNs, respectively. Additionally, the DMNs demonstrated no cytotoxicity toward L929 cells and displayed hemocompatibility. Overall, the developed supramolecular DMNs system presents a promising approach for enhancing the transdermal delivery of AZA, with the potential to enhance therapeutic outcomes in acne treatment.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107108"},"PeriodicalIF":4.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230509","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":"Effect of inlet swirl on dry powder distribution through the oropharyngeal route of human respiratory tract","authors":"Anurag Tiwari , Akshoy Ranjan Paul , Anuj Jain","doi":"10.1016/j.jddst.2025.107097","DOIUrl":"10.1016/j.jddst.2025.107097","url":null,"abstract":"<div><div>This study utilized computational fluid dynamics (CFD) to investigate the impact of swirling airflow on dry powder drug particle transport and deposition in a realistic human respiratory tract model extending from the oral cavity to the sixth bronchial bifurcation. The model incorporated steady-state inspiratory flow conditions and discrete phase modeling to simulate the behavior of 1 μm–25 μm particles at various flow rates (5–45 L/min), swirl numbers (SN = 0, 0.25, 0.4, 0.85), and swirl directions (clockwise [CW] and anticlockwise [ACW]).</div><div>The results demonstrated that moderate swirling flow improves drug targeting in the distal lung. Specifically, a CW swirl at Sn = 0.4 with a low flow rate of 10 L/min achieved the most efficient deposition, delivering approximately 75 % of 5 μm particles to the distal region, while minimizing unwanted deposition in the oropharyngeal region. At a standard condition of 30 L/min and 1 μm particles, a CW swirl at SN = 0.4 yielded the highest in the distal region deposition (51.37 %) compared to only 23.97 % in the no-swirl case.</div><div>Flow visualization confirmed that the swirl promotes favorable jet redirection and enhanced particle residence time, while maintaining wall shear stress within physiologically safe limits. Excessive swirl (SN = 0.85) increased deposition in the oropharyngeal region, due to inertial impaction. These findings highlight the potential of controlled swirl, especially CW swirl at low flow rates, as a practical strategy to improve DPI design for targeted pulmonary drug delivery.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107097"},"PeriodicalIF":4.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189993","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":"Site-specific delivery of pectin-stabilized gold nanoparticles for liver: An in vivo evaluation with Doxorubicin","authors":"Mayank Kumar Singh , Sophia Mckenzie Schulte , Rohith Kumar , Shilpa Kumar , Swati Singh , Abhay Singh Chauhan","doi":"10.1016/j.jddst.2025.107118","DOIUrl":"10.1016/j.jddst.2025.107118","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is the most common (80–85%) form of liver cancer. Doxorubicin (DOX) is a well-known highly potent anti-cancer drug but still lags due to its formulation, stability issues and other physicochemical properties leading to suboptimal performance. The use of gold nanoparticles as a drug delivery system has become one of the most promising strategies, especially in areas like cancer therapy where targeted and controlled drug release is crucial. We have developed an advanced gold nanoparticle (GNP) system using natural polysaccharide (Pectin). The dual functionality of pectin works as a stabilizer for GNP and also ensures liver-specific drug delivery via Asialoglycoprotein (ASGP) receptors expressed on the surface of liver cells. The present study aims to synthesize, characterize and explore the potential of pectin-stabilized gold nanoparticles (P-GNP) using DOX for liver targeting (in vivo). The P-GNP-DOX hydrodynamic diameter was 99.80±2.21 nm, which was further corroborated by AFM. UV–visible spectroscopy indicated molecular interactions between DOX and P-GNP through characteristic red-shifts in the surface plasmon resonance band. Electrostatic interaction was also evidenced by FT-IR and 1H NMR. The P-GNP-DOX demonstrated prolonged in vitro drug release and better stability profile in physiological conditions compared to its commercially available Doxotero® Injection. The targeting efficiency of the P-GNP-DOX was evaluated in preclinical (living animal) studies using a non-invasive in vivo imaging system. The P-GNP-DOX showed better liver targeting potential compared to the DOX alone. It is the first preclinical in vivo study of pectin-stabilized gold nanoparticles and results indicate that it could be a promising platform for the liver targeting.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107118"},"PeriodicalIF":4.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204681","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}