International Journal of Pharmaceutics: X最新文献

{"title":"Liposomal glytrexate formulation: improving antitumour efficacy and minimizing toxicity in breast cancer therapy","authors":"Wenli He ,&nbsp;Meng Yan ,&nbsp;Yue Li ,&nbsp;Jianchao Wang ,&nbsp;Jianing Yang ,&nbsp;Chaoxing He ,&nbsp;Shaokun Yang ,&nbsp;Deying Cao ,&nbsp;Jing Bai ,&nbsp;Lei Wang ,&nbsp;Bai Xiang","doi":"10.1016/j.ijpx.2025.100356","DOIUrl":"10.1016/j.ijpx.2025.100356","url":null,"abstract":"<div><div>Cancer remains a critical global health challenge with increasing incidence rates. This study reports the first successful encapsulation of glytrexate (GTX), a novel 6-substituted-pyrrolo [2,3-d] pyrimidine compound, into liposomes. This innovative formulation increases the stability, half-life, and bioavailability of GTX while significantly reducing toxicity. GTX liposomes, with a uniform spherical shape and an average particle size of 121.7 ± 2.9 nm, demonstrated a satisfactory encapsulation efficiency (24.2 ± 0.99 %). Compared to the free drug, GTX liposomes exhibited significantly enhanced inhibitory effects on 4 T1, A549, and MCF-7 cells in vitro. The pharmacokinetic analysis showed prolonged circulation (T_1/2: 3.82 h vs. 1.86 h) and increased systemic exposure (AUC_0–∞: 31975.79 vs. 11,545.86 μg·h/L). In vivo studies further confirmed their efficacy, as they substantially reduced tumour growth by 50 %, decreasing lung metastasis in 4 T1 cell models, and minimizing GTX-related side effects. These findings highlight the potential of liposomal GTX formulations to improve breast cancer treatment outcomes.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100356"},"PeriodicalIF":5.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and characterization of fenticonazole nitrate-loaded cubogel for the management of vaginal candidiasis","authors":"Sadek Ahmed ,&nbsp;Osama Saher ,&nbsp;Heba Attia ,&nbsp;Abdurrahman M. Fahmy ,&nbsp;Islam M. Adel","doi":"10.1016/j.ijpx.2025.100355","DOIUrl":"10.1016/j.ijpx.2025.100355","url":null,"abstract":"<div><div>Vaginal candidiasis is a medical condition that affects large majority of the women at least once in their lifetime. The condition manifests with itching, irritation, and discharges which is troublesome for women during mundane activities. The purpose of this research was to formulate and evaluate the physicochemical properties and drug permeation of Fenticonazole-loaded cubogel through vaginal mucosa. Concisely, the drug-loaded cubosomes were prepared via hot dispersion emulsification technique. Following, the percent drug entrapment efficiency, particle size, polydispersity index, and zeta potential of the cubosomes were determined. Optimization criteria involved maximizing entrapment efficiency (EE %) and zeta potential (ZP), while maintaining a nanoscale particle size to ensure colloidal stability. The optimized formulation exhibited a high desirability score of 0.933 with EE % of 85.32<span><math><mo>±</mo></math></span>2.34 %, PS of 169<span><math><mo>±</mo></math></span>0.85 nm, PDI of 0.29<span><math><mo>±</mo></math></span>0.02, and ZP of −24.40<span><math><mo>±</mo></math></span>1.27 mV. In addition, 86.77<span><math><mo>±</mo></math></span>3.79 % of Fenticonazole nitrate was released from the optimum cubosomal formulation after 8 h. Cubical nanovesicles were revealed via transmission electron microscope while infrared spectroscopy revealed the lack of interaction between the used components. Stability was unchanged upon storage for three months. The rheogram of the optimum formulation-loaded cubogel suggested a shear-thinning behavior. Additionally, the optimum cubogel demonstrated higher biofilm inhibitory effect compared to the drug suspension. Similarly, both, ex vivo permeation and confocal laser scanning, suggested the enhanced vaginal epithelium permeability and the deeper vaginal mucosa penetration of the optimum cubogel, compared to the drug suspension and aqueous Rhodamine B carbopol gel, respectively. Histopathological assessment concluded with the safety of the cubogel on the vaginal mucosal epithelium and underlying tissue.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100355"},"PeriodicalIF":5.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing losartan potassium against rheumatoid arthritis via transdermally-delivered leciplexes: Accentuated efficacy through modulation of angiotensin II/AT1R/AT2R axis","authors":"Amira A. Hussein ,&nbsp;Basmah N. Aldosari ,&nbsp;Randa M. Zaki ,&nbsp;Obaid Afzal ,&nbsp;Adel A. Ali ,&nbsp;Heba M. Aboud ,&nbsp;Yasmin M. Ahmed ,&nbsp;Demiana M. Naguib","doi":"10.1016/j.ijpx.2025.100354","DOIUrl":"10.1016/j.ijpx.2025.100354","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory ailment which preferentially impacts the synovial membranes of joints and ultimately triggers cartilage and bone erosion. Angiotensin II (Ang II) participates in the pathogenesis of RA; hence, Ang II receptor blockade, accomplished through a specific inhibitor such as losartan potassium (LST), may confer an effective therapeutic avenue for RA. This study aimed to develop, optimize, and characterize LST-loaded leciplexes (LST-LPXs) to ameliorate its bioavailability and prolong its therapeutic efficacy for combating RA. To accomplish this objective, LST-LPX dispersions were assembled through a single-step process and optimized via D-optimal design for various physicochemical traits employing Design-Expert® software. Also, pharmacokinetic studies were explored in rats. Additionally, in complete Freund's adjuvant-induced RA in Wistar rats, RF, COMP, NADPH oxidase, NO, IL-6, TNF-α, besides Ang II and its receptors (AT1R &amp; AT2R) were measured. The optimum LST-LPXs formulation elicited acceptable entrapment efficiency (88.05%), nano-scaled spherical morphology (246.71 nm), controlled release over 24 h (86.33%), and adequate permeation properties through the skin (417.83 μg/cm²). The pharmacokinetic analysis disclosed a snowballed bioavailability of the optimized LST-LPXs gel by 3.08- and 1.2-fold versus the oral solution and crude gel, respectively. The optimum LST-LPXs gel divulged accentuated anti-arthritic effects, evidenced by significant suppression of rheumatoid, oxidative stress, and inflammatory biomarkers coupled with corrections of AT1R and AT2R protein expression. Practically, the current findings proposed a compelling proof-of-principle that the transdermal LST-LPXs could serve as a non-invasive promising nanoparadigm for RA tackling.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100354"},"PeriodicalIF":5.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticle technologies in precision oncology and personalized vaccine development: Challenges and advances","authors":"Saber Imani ,&nbsp;Samaneh Moradi ,&nbsp;Tola Abdulsattar Faraj ,&nbsp;Pejman Hassanpoor ,&nbsp;Nazanin Musapour ,&nbsp;Soran K. Najmaldin ,&nbsp;Anno Hashm Abdulhamd ,&nbsp;Aliasghar Tabatabaei Mohammadi ,&nbsp;Chnar Husam Taha ,&nbsp;Sargol Aminnezhad","doi":"10.1016/j.ijpx.2025.100353","DOIUrl":"10.1016/j.ijpx.2025.100353","url":null,"abstract":"<div><div>Nanoparticles (NPs) are changing the paradigm of precision oncology by providing means for targeted delivery, immune modulation, and personalized therapies for patients. To this end, drug delivery systems (DDS) have improved the precision in precision medicine and improved the design, delivery, and targeting of immune interventions through the use of NPs. This review aims to address the most clinically relevant NP platforms, including lipid (LNPs), polymeric (PNPs), metal-based (MNPs), ceramic (CNPs), carbon-based (CBNs), aptamer conjugated (ANPs), and quantum dots (QDs), and reviewed as potential therapeutic and diagnostic applications and their utility in oncology. Further, we will touch on next-generation systems, including hybrid NPs (HNPs), stimulus-response NPs (SRNPs), and artificial-intelligence (AI) directed NPs (AI-NPs) that are programmable and adaptive with precision-engineered capabilities for cancer vaccinations and immunotherapy. We will discuss how NPs function as a DDS and how these systems facilitate controlled antigen release, better delivery to antigen-presenting cells, and the delivery of neoantigen-based immunotherapies. The ability of NPs to support cell-based therapies, including CAR-T cells, and help overcome multi-drug resistant (MDR) is also explored. Although obstacles remain regarding the development of scalable, safe, and regulatory approved therapies, the ongoing progress in the field of nanomedicine suggests new strategies enabling the delivery of efficient personalized anticancer therapies with clinical benefits for cancer patients.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100353"},"PeriodicalIF":5.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative study on two kinds of brain-targeted liposomes co-modified by RVGP and R9 in different ways","authors":"Yu Hei ,&nbsp;Xin Wang ,&nbsp;Yang Chen ,&nbsp;Zi Mei ,&nbsp;Xuebing Yang ,&nbsp;ZhaoShuai Ji ,&nbsp;Ying Xie","doi":"10.1016/j.ijpx.2025.100352","DOIUrl":"10.1016/j.ijpx.2025.100352","url":null,"abstract":"<div><div>With the global aging population and rising tumor incidence, central nervous system degenerative diseases and brain tumors have emerged as critical threats to human health. Leveraging the biological properties of the blood-brain barrier (BBB), the development of dual-mediated brain-targeted liposomes via receptor-mediated and adsorption-mediated mechanisms holds promise for overcoming limitations such as lysosomal entrapment and saturation in single-receptor systems, thereby enabling efficient brain drug delivery. In this study, we constructed two types of dual-mediated liposomes using the BBB-specific ligand RVGP and cell-penetrating peptide R9 through distinct strategies: the monoligand liposome RVGPR9-SSL (incorporating both ligands as a single conjugate) and the biligand liposome RVGP-R9-SSL (displaying ligands as separate moieties). An in-depth comparative analysis of their BBB permeability and transport mechanisms was performed. Results demonstrate that RVGPR9-SSL circumvents lysosomal degradation via an endoplasmic reticulum-mediated transport pathway, exhibiting superior brain-targeted delivery efficiency and an excellent safety profile. These findings establish RVGPR9-SSL as an efficient brain-targeted drug delivery system with broad therapeutic potential for central nervous system disorders. Moreover, this study provides critical insights for the rational design of next-generation dual-mediated brain-targeted liposomal systems.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100352"},"PeriodicalIF":5.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the plasticity of dry granulated particles (mini-tablets) and its relationship to their tabletability","authors":"Maryam Tofiq,&nbsp;Göran Alderborn,&nbsp;Josefina Nordström,&nbsp;Ann-Sofie Persson","doi":"10.1016/j.ijpx.2025.100351","DOIUrl":"10.1016/j.ijpx.2025.100351","url":null,"abstract":"<div><div>Mini-tablets of different proportions of <em>α</em>-lactose monohydrate (LAC) and microcrystalline cellulose (MCC) were prepared by uniaxial compaction and served as surrogate granules. The inverted Adams coefficient i.e., <em>α</em>⁻¹ was derived from bulk mini-tablet compression data and used as an indication of granule plastic deformation. The correlation of the parameter to single granule deformability assessed from uniaxial single mini-tablet compression and macro-indentation hardness was investigated. Furthermore, the relationship between the plastic deformation parameters and the tabletability of mini-tablets were evaluated. An increased MCC concentration resulted in an increased indentation hardness and deformability of the mini-tablets, but no correlation was found between indentation hardness and the <em>α</em>⁻¹ coefficient. Thus, the plastic deformation expressed during powder compression showed no relationship to the single specimen indentation hardness and plastic deformability. An increased indentation hardness tended to correspond to an increased tablet tensile strength, while the opposite applied for the <em>α</em>⁻¹ coefficient. The trend of increased tablet tensile strength with higher MCC concentration was broken at the highest MCC concentration, i.e., for mini-tablets showing very limited fragmentation. It was concluded that granule plastic deformation is a key property for granule tabletability. It is suggested that granule plastic deformation should be assessed during granule engineering.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100351"},"PeriodicalIF":5.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ionic liquids self-assembled micelles for transdermal delivery: characterization, functions and applications","authors":"Ziqing Deng ,&nbsp;Shuwei Tang ,&nbsp;Mingjie Ou ,&nbsp;Zhuxian Wang","doi":"10.1016/j.ijpx.2025.100350","DOIUrl":"10.1016/j.ijpx.2025.100350","url":null,"abstract":"<div><div>Ionic liquid (ILs) self-assembled micelles (ILs-SAMs) are promising and effective drug delivery systems, which combine the merits of ILs and micelles. Herein, the properties, assembly, functions, and treatments of ILs-SAMs in transdermal drug delivery are summarized. This paper first reviews the fundamental concepts, classifications, assembly mechanisms, characterization techniques, and functional roles of ILs-SAMs. ILs-SAMs are micellar structures formed by the self-assembly of ILs through different intermolecular interactions, and are affected by multiple environmental factors. They possess unique physicochemical properties, endowing them with high stability and effective drug carriers, which could regulate their compositions and structures for flexible and controllable characteristics. Next, the review demonstrates that ILs-SAMs offer remarkable advantages in transdermal delivery, including solubilization enhancement, permeation enhancement, and targeted transdermal delivery. It alters the surface tension and viscosity of permeating substances, facilitates transdermal drug penetration, and utilizes nanoscale properties for precise, targeted delivery. Remarkably, ILs-SAMs were compared with other ILs self-assembled nanoparticles (ILs-SANPs) and polymer micelles, and the former possessed superior properties, including easier self-assembly and higher stability. Lastly, it focuses on their applications in treating skin cancer, arthritis, diabetes, fungal infections, and skin photoaging. Collectively, the novel ILs-SAMs are multifunctional transdermal drug delivery systems used for permeation enhancement, targeted drug delivery and different skin disorders.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100350"},"PeriodicalIF":5.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-derived extracellular vesicles as a natural drug delivery platform for glioblastoma therapy: A dual role in preserving endothelial integrity while modulating the tumor microenvironment","authors":"Lishan Cui ,&nbsp;Giordano Perini ,&nbsp;Antonio Minopoli ,&nbsp;Valentina Palmieri ,&nbsp;Marco De Spirito ,&nbsp;Massimiliano Papi","doi":"10.1016/j.ijpx.2025.100349","DOIUrl":"10.1016/j.ijpx.2025.100349","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most aggressive primary brain tumor, with limited treatment options due to the restrictive blood-brain barrier (BBB) and the heterogeneity of the blood-tumor barrier (BTB). Temozolomide (TMZ), the standard chemotherapy, suffers from poor BBB permeability, rapid degradation, and systemic toxicity. Plant-derived extracellular vesicles (PDEVs) have emerged as promising natural nanocarriers, offering biocompatibility, stability, and the ability to cross biological barriers. This study investigates the use of extracellular vesicles from <em>Citrus limon</em> L. (LDEs) to encapsulate and deliver TMZ (EVs@TMZ) for GBM treatment.</div><div>LDEs were isolated, characterized, and loaded with TMZ via ultrasonication. Encapsulation efficiency, stability, and physicochemical properties were assessed using UV–Vis and FTIR spectroscopy. A 3D BTB model was developed using bioprinted U87 glioblastoma cells in Matrigel, co-cultured with hCMEC/D3 endothelial cells to replicate the tumor microenvironment. Barrier integrity was evaluated through TEER and FITC-dextran assays. Uptake, cytotoxicity, and tumor invasion were assessed in this model, along with oxidative stress and VEGF-A secretion.</div><div>LDEs effectively encapsulated TMZ, enhancing drug stability under physiological conditions. EVs@TMZ crossed the endothelial barrier while preserving barrier integrity and reducing TMZ-induced ROS production. In the 3D glioblastoma model, EVs@TMZ showed strong cytotoxic effects on tumor cells while minimizing endothelial toxicity and oxidative stress. Moreover, VEGF-A secretion was suppressed, disrupting pro-tumorigenic pathways.</div><div>These findings highlight Citrus-derived EVs as biocompatible, efficient carriers for TMZ delivery, offering a promising approach to overcome current challenges in GBM therapy and supporting further development of PDEVs for brain tumor treatment.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100349"},"PeriodicalIF":5.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic photodynamic and chemodynamic therapy using hypoxia-adaptive Ce6@Co nanoparticles for enhanced tumor suppression","authors":"Yeji Chang,&nbsp;Yong Geun Lim,&nbsp;Kyeongsoon Park","doi":"10.1016/j.ijpx.2025.100348","DOIUrl":"10.1016/j.ijpx.2025.100348","url":null,"abstract":"<div><div>Conventional photodynamic therapy (PDT) is less effective in solid tumors owing to Type-II PDT mechanism's reliance on oxygen (O₂), which is scarce in hypoxic environments. Most hydrophobic photosensitizers have poor water solubility, complicating their formulation and delivery. To address these challenges, Ce6@Co nanoparticles (a hypoxia-adaptive nanoplatform) were developed via coordinating Co²⁺ ions with chlorin e6 (Ce6), exhibiting uniform size (∼230 nm), enhanced dispersibility, and colloidal stability. These nanoparticles generate dual-mode reactive oxygen species (ROS): Type-II ¹O₂ via PDT under 670 nm irradiation and oxygen-independent hydroxyl radical (⋅OH) via Co²⁺-mediated Fenton-like reactions. In vitro, Ce6@Co nanoparticles demonstrated superior cellular uptake and robust ROS amplification, and reduced squamous cell carcinoma (SCC7) cell viability to 34.4 % under normoxia and 20.48 % under hypoxia via synergistic photodynamic and chemodynamic (PDT-CDT) effects, causing considerable apoptosis. In vivo, intratumoral administration of Ce6@Co nanoparticles via laser irradiation completely suppressed tumors in SCC7 tumor-bearing mice. This effect was attributed to favorable intratumoral distribution, enhanced retention, and synergistic PDT-CDT. No systemic toxicity was observed, as indicated by stable body weight, normal serum biomarkers, and unchanged organ histology. The Co²⁺-coordinated photosensitizer system uses hypoxia-elevated H₂O₂ to sustain CDT, effectively overcoming conventional PDT's oxygen dependence and offering a safe and effective dual-modal therapeutic strategy for hypoxic solid tumors.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100348"},"PeriodicalIF":5.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an inhalable dry powder formulation for inhibition of SARS-CoV-2","authors":"Justin Stella ,&nbsp;Anja Germann ,&nbsp;Oliver Janka ,&nbsp;Sylvia Wagner ,&nbsp;Marc Schneider","doi":"10.1016/j.ijpx.2025.100346","DOIUrl":"10.1016/j.ijpx.2025.100346","url":null,"abstract":"<div><div>Coronaviruses, including SARS-CoV-2, can cause significant lung damage and may result in multiple organ failure. The severity of COVID-19 is determined by the virus's entry into lung tissue and subsequent replication. This entry is facilitated by the angiotensin-converting enzyme 2 (ACE2) in combination with the serine protease TMPRSS2, which is a critical step. To reduce viral replication, it is necessary to prevent the uptake of the virus directly at the main route of transmission, which is the deposition of the virus as an aerosol in the respiratory tract. To reduce viral uptake into lung cells, an inhalable dry powder formulation was developed. The formulation contains camostat, a clinically proven serine protease inhibitor that inhibits the cellular uptake mechanisms on the lung surface. Camostat was spray-dried together with the mucolytic agent <em>N</em>-acetylcysteine to produce co-amorphous microparticles with sufficient solubility after deposition. Microparticles with properties suited for deposition in the deep part of the respiratory tract can be produced by using appropriate spray-drying parameters. The use of L-leucine enabled suitable aerodynamic properties and storage stability due to reduced interaction with environmental water. The geometric particle diameter, determined using laser light diffraction, decreased with L-leucine content which was found forming a partially crystalline L-leucine shell. The disintegration behavior of the microparticle formulation simulated under lung-like conditions indicated fast disintegration. A pseudo-viral <em>in vitro</em> assay demonstrated low acute toxicity in combination with a high activity. Cell viability and proliferation were not affected by camostat concentrations up to 11.1 μg/mL. The IC₅₀ values of the two dry powder formulations tested on a HEK293T/ACE2-TMPRSS2 cell line were 0.008 μg/mL and 0.019 μg/mL, respectively, which is at least 100 times lower than the cytotoxic concentration. This dry powder formulation serves as a prototype microparticle matrix for incorporating nanoscale drug carriers in the future.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100346"},"PeriodicalIF":5.2,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}