Drug Delivery and Translational Research最新文献

{"title":"Volumetric printing and non-destructive drug quantification of water-soluble supramolecular hydrogels.","authors":"Jun Jie Ong, Anna Kirstine Jørgensen, Zilan Zhu, Richard Telford, Philip J Davies, Simon Gaisford, Alvaro Goyanes, Abdul W Basit","doi":"10.1007/s13346-024-01723-6","DOIUrl":"https://doi.org/10.1007/s13346-024-01723-6","url":null,"abstract":"<p><p>Vat photopolymerisation 3D printing is being actively explored for manufacturing personalised medicines due to its high dimensional accuracy and lack of heat application. However, several challenges have hindered its clinical translation, including the inadequate printing speeds, the lack of resins that give soluble matrices, and the need for non-destructive quality control measures. In this study, for the first time, a rapid approach to producing water-soluble vat photopolymerised matrices and a means of non-destructively verifying their drug content were investigated. Volumetric printing, a novel form of vat photopolymerisation, was used to fabricate personalised warfarin-loaded 3D-printed tablets (printlets). Eight different formulations containing varying amounts of warfarin (0.5-6.0% w/w) were used to print two different sized torus-shaped printlets within 6.5 to 11.1 s. Nuclear magnetic resonance (NMR) spectroscopy revealed the presence of only trace amounts of unreacted acrylate monomers, suggesting that the photopolymerisation reaction had occurred to near completion. All printlets completely solubilised and released their entire drug load within 2.5 to 7 h. NIR spectroscopy (NIRS) was used to non-destructively verify the dose of warfarin loaded into the vat photopolymerised printlets. The partial least square regression model built showed strong linearity (R² = 0.980), and high accuracy in predicting the drug loading of the test sample (RMSEP = 0.205%). Therefore, this study advances pharmaceutical vat photopolymerisation by demonstrating the feasibility of producing water-soluble printlets via volumetric printing and quantifying the drug load of vat photopolymerised printlets with NIRS.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460457","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":"Correction: Simultaneous therapeutic and diagnostic applications of magnetic PLGA nanoparticles loaded with doxorubicin in rabbit.","authors":"Zahra Salmasi, Hossein Kamali, Hanieh Rezaee, Faezeh Nazeran, Zahra Jafari, Frarhad Eisvand, Manouchehr Teymouri, Elnaz Khordad, Jafar Mosafer","doi":"10.1007/s13346-024-01725-4","DOIUrl":"https://doi.org/10.1007/s13346-024-01725-4","url":null,"abstract":"","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460530","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":"Targeted lipid nanoparticles to prevent trans-placental passage in the ex vivo human placental cotyledon perfusion model.","authors":"Caren van Kammen, Hedwig van Hove, Dimitrios Kapsokalyvas, Rick Greupink, Raymond Schiffelers, Titia Lely, Fieke Terstappen","doi":"10.1007/s13346-024-01715-6","DOIUrl":"https://doi.org/10.1007/s13346-024-01715-6","url":null,"abstract":"<p><p>Medication use during pregnancy poses risks to both the mother and the fetus. These risks include an elevated potential for fetotoxicity due to placental drug transport. Nanomedicines offer a promising solution by potentially preventing trans-placental passage. Targeted nanomedicines could enhance safety and efficacy in treating maternal or placental pathophysiology. Our study investigates placental transfer kinetics of targeted lipid nanoparticles (LNPs) in an ex vivo human placenta cotyledon perfusion model. We collected human placentas for dual-side ex vivo placental perfusions. Targeted LNPs with a fluorescence tag were introduced into the maternal circuit of each placenta. To establish if there was trans-placental passage of LNPs to the fetal circuit, we collected samples from maternal and fetal circuits throughout the six hours of the perfusion. We determined the fluorescence signal using a multi-mode microplate reader and Multiphoton microscopy to localize the LNPs in the placenta tissue. Data from perfused placenta tissue showed no significant transfer of the fluorescently labeled LNPs across the placental barrier to the fetal circuit. Localization of targeted LNPs in tissue samples is mainly observed in the maternal blood space of the placenta. Our results suggest that targeted LNPs present a promising strategic approach to prevent trans-placental passage to the fetus. Our future perspectives involve investigating the efficacy of targeted LNPs as well as loading targeted LNPs with nucleic acid-based therapeutics to investigate their therapeutic potential.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460456","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":"Sustained release of proteins from contact lenses with porous annulus.","authors":"Zachary Sparks, Anuj Chauhan","doi":"10.1007/s13346-024-01720-9","DOIUrl":"https://doi.org/10.1007/s13346-024-01720-9","url":null,"abstract":"<p><p>Ophthalmic drugs are administered to the front of the eye by eyedrops. The bioavailability of drugs delivered via eye drops is low due to tear turnover. Contact lenses can address some deficiencies of eye drops by sustaining the delivery of drugs, but commercial contact lenses have small pore sizes that cannot load biologics, which are becoming more common for treating ophthalmic diseases. This study aims to investigate novel poly(hydroxyethyl methacrylate) (pHEMA) lenses with transparent center and porous annulus for sustained release of model proteins. A novel hydrogel polymerization process was used to fabricate concentric, porous layer pHEMA hydrogel rods. The hydrogels were lathe cut into contact lenses which were explored for the delivery of proteins and gold nanoparticles. Lenses were characterized by partition coefficient and diffusivity, which was estimated by fitting experimental data to an analytical model. Transmittance measurements were made to compare transparency of porous lens centers to commercial contact lenses. Porous pHEMA lenses consisting of a concentric, porous layer made from 55% water content in precursor were successfully lathe cut into lenses with transparent center and opaque porous annulus. The porous lenses could load large model proteins of bovine serum albumin and human γ-globulin and provide sustained release. The core annular pHEMA contact lenses consisting of an outer annulus of opaque, porous pHEMA and an inner, center layer of clear, nonporous pHEMA can provide sustained delivery of biologics.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460455","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":"Auranofin loaded silk fibroin nanoparticles for colorectal cancer treatment.","authors":"Marta Pérez-Lloret, Eileen Reidy, Antonio Abel Lozano-Pérez, Juan A Marchal, Piet N L Lens, Aideen E Ryan, Andrea Erxleben","doi":"10.1007/s13346-024-01719-2","DOIUrl":"https://doi.org/10.1007/s13346-024-01719-2","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the second most common cause of cancer related deaths worldwide and the prevalence in young people especially is increasing annually. In the search for innovative approaches to treat the disease, drug delivery systems (DDS) are promising owing to their unique properties, which allow improved therapeutic results with lower drug concentrations, overcoming drug resistance and at the same time potentially reducing side effects. Silk fibroin is a biopolymer that can be processed to obtain biocompatible and biodegradable nanoparticles that can be efficiently loaded by surface adsorption with small-molecule therapeutics and allow their transport and sustained release by modulating their pharmacokinetics. Auranofin (AF) has recently been repurposed for its strong anticancer activity and is currently in clinical trials. Its mechanism of action is through the inhibition of thioredoxin reductase enzymes, which play an essential role in several intracellular processes and are overexpressed in some tumours. Taking into account that AF has a low solubility in water, we propose silk fibroin nanoparticles (SFN) as AF carrier in order to improve its bioavailability, increasing cellular absorption and preventing its degradation or avoiding some resistance mechanisms. Here we report the preparation and characterization of a new formulation of AF-loaded silk fibroin nanoparticles (SFN-AF), its functionalization with FITC for the analysis of cellular uptake, as well as its cytotoxic activity against cell lines of human colorectal cancer (HT29 and HCT116) in both 2D and 3D cell cultures. 3D spheroid models provide a 3D environment which mimics the 3D aspects of CRC observed in vivo and represents an effective 3D environment to screen therapeutics for the treatment of CRC. The loaded nanoparticles showed a spherical morphology with a hydrodynamic diameter of ~ 160 nm and good stability in aqueous solution due to their negative surface charges. FESEM-EDX analysis revealed a homogeneous distribution of Au clusters with high electron density on the surface of the nanoparticles. SFN-AF incubated in phosphate buffer at 37 °C released 77% of the loaded AF over 10 days, showing an initial burst and then sustained release. Flow cytometry analysis showed that FITC-SFN-AF was efficiently internalized by both cell lines, which was confirmed by confocal microscopy imaging. SFN enhanced the cytotoxicity of AF in 2D cultures in both CRC lines. Promising results were also obtained in 3D culture paving the way for future application of this strategy as a therapy for CRC.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388862","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":"Clinical translation and landscape of silver nanoparticles.","authors":"Manuel Dias, Rui Zhang, Twan Lammers, Roger M Pallares","doi":"10.1007/s13346-024-01716-5","DOIUrl":"https://doi.org/10.1007/s13346-024-01716-5","url":null,"abstract":"<p><p>Despite being clinically used for over a century, the benefits of silver nanoparticles are perennially under debate and dispute. In the last two decades, a revived interest in their therapeutic applications has resulted in a few new formulations transitioning into clinical trials. These metal nanomedicines are used in concrete applications that are defined by the physicochemical and biological features of the silver nanoconstructs, as well as their biodistribution profiles. Examples of these applications are topical antibacterial and antiviral therapies and wound healing, as these avoid concerns regarding the long-term accumulation of the nanomedicines in fenestrated organs after intravenous administration. Here, we discuss the current landscape of silver nanoparticles, and critically analyze the characteristics that endowed their transition and use in clinical settings.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388863","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":"Correction: Bcl-2 knockdown by multifunctional lipid nanoparticle and its influence in apoptosis pathway regarding cutaneous melanoma: in vitro and ex vivo studies.","authors":"Juliana Santos Rosa Viegas, Jackeline Souza Araujo, Marcel Nani Leite, Fabiola Garcia Praça, Jose Orestes Del Ciampo, Enilza Maria Espreáfico, Marco Andrey Cipriani Frade, Maria Vitória Lopes Badra Bentley","doi":"10.1007/s13346-024-01717-4","DOIUrl":"https://doi.org/10.1007/s13346-024-01717-4","url":null,"abstract":"","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375252","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":"The penetration efficiency of a dissolved model drug into hair follicles depends on the concentration of added nanoparticles.","authors":"Loris Busch, Darya Asadzadeh, Anna Lena Klein, Phuvamin Suriyaamporn, Mont Kumpugdee Vollrath, Cornelia M Keck, Martina C Meinke","doi":"10.1007/s13346-024-01718-3","DOIUrl":"https://doi.org/10.1007/s13346-024-01718-3","url":null,"abstract":"<p><p>Hair follicles have recently emerged as promising drug delivery targets and gates for skin penetration. The so-called ratchet effect, which is based on an interaction between the hair shaft surface, the intrafollicular stratum corneum and nanoparticles, has proven to be very effective for the transport of active ingredients. Especially the nanoparticle-assisted decolonization of hair follicles constitutes an interesting new area of application. In a recently published work it was shown that small molecules as well as macromolecules solved in an outer phase of a formulation can be transported into the deeper parts of the hair follicles by adding nanoparticles to the formulation. In this case the nanoparticles constitute an entity independent of the drug and the transport is hypothesized to be based on an adhesion effect. In the present work, we focused on the impact of the particle concentration in the formulation on the transport efficiency of the model drug fluorescein sodium into hair follicles utilizing an ex vivo porcine skin model. It was observed that a particle concentration of 4% significantly enhances the transport efficiency of fluorescein as compared to 2% particle concentration. Doubling the concentration to 8% did not significantly increase the penetration depth. The effect evolved more efficiently when using 4 Hz circular motion massage as compared to 100 Hz oscillating massage. These results deliver interesting information on the optimal formulation as well as application parameters for a future application in clinical studies for e.g. skin antisepsis purposes.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371295","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":"Multi-loaded PLGA microspheres as neuroretinal therapy in a chronic glaucoma animal model.","authors":"Alba Aragón-Navas, Maria Jesus Rodrigo, Inés Munuera, David García-Herranz, Manuel Subías, Pilar Villacampa, Julián García-Feijoo, Luis Pablo, Elena Garcia-Martin, Rocio Herrero-Vanrell, Irene Bravo-Osuna","doi":"10.1007/s13346-024-01702-x","DOIUrl":"https://doi.org/10.1007/s13346-024-01702-x","url":null,"abstract":"<p><p>This work focused on the co-encapsulation and simultaneous co-delivery of three different neuroprotective drugs in PLGA (poly(lactic-co-glycolic acid) microspheres for the treatment of glaucoma. For formulation optimization, dexamethasone (anti-inflammatory) and ursodeoxycholic acid (anti-apoptotic) were co-loaded by the solid-in-oil-in-water emulsion solvent extraction-evaporation technique as a first step. The incorporation of a water-soluble co-solvent (ethanol) and different amounts of dexamethasone resulted critical for the encapsulation of the neuroprotective agents and their initial release. The optimized formulation was obtained with 60 mg of dexamethasone and using an 80:20 dichloromethane:ethanol ratio. In the second step in the microencapsulation process, the incorporation of the glial cell line-derived neurotrophic factor (GDNF) was performed. The final prototype showed encapsulation efficiencies for each component above 50% with suitable properties for long-term application for at least 3 months. Physicochemical studies were performed by SEM, TEM, DSC, XRD, and gas chromatography. The evaluation of the kinetic release by the Gallagher-Corrigan analysis with Gorrasi correction helped to understand the influence of the co-microencapsulation on the delivery of the different actives from the optimized formulation. The final prototype was tested in a chronic glaucoma animal model. Rats received two intravitreal injections of the neuroprotective treatment within a 24-week follow-up study. The proposed formulation improved retinal ganglion cell (RGC) functionality examined by electroretinography. Also, it was able to maintain a neuroretinal thickness similar to that of healthy animals scanned by in vivo optical coherence tomography, and a higher RGC count on histology compared to glaucomatous animals at the end of the study.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364794","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":"Unlocking the potential of nanomedicine: advances in precision targeting strategies.","authors":"Christian Celia, Tambet Teesalu, Hélder A Santos","doi":"10.1007/s13346-024-01686-8","DOIUrl":"10.1007/s13346-024-01686-8","url":null,"abstract":"","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2593-2597"},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878494","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}