nanoparticle dissolution
Dotaz
Zobrazit nápovědu
The utilization of 3D printing- digital light processing (DLP) technique, for the direct fabrication of microneedles encounters the problem of drug solubility in printing resin, especially if it is predominantly composed of water. The possible solution how to ensure ideal belonging of drug and water-based printing resin is its pre-formulation in nanosuspension such as nanocrystals. This study investigates the feasibility of this approach on a resin containing nanocrystals of imiquimod (IMQ), an active used in (pre)cancerous skin conditions, well known for its problematic solubility and bioavailability. The resin blend of polyethylene glycol diacrylate and N-vinylpyrrolidone, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photoinitiator, was used, mixed with IMQ nanocrystals in water. The final microneedle-patches had 36 cylindrical microneedles arranged in a square grid, measuring approximately 600 μm in height and 500 μm in diameter. They contained 5wt% IMQ, which is equivalent to a commercially available cream. The homogeneity of IMQ distribution in the matrix was higher for nanocrystals compared to usual crystalline form. The release of IMQ from the patches was determined ex vivo in natural skin and revealed a 48% increase in efficacy for nanocrystal formulations compared to the crystalline form of IMQ.
- MeSH
- 3D tisk * MeSH
- aplikace kožní MeSH
- imichimod * chemie aplikace a dávkování MeSH
- jehly * MeSH
- kožní absorpce MeSH
- kůže metabolismus MeSH
- lékové transportní systémy přístrojové vybavení MeSH
- mikroinjekce přístrojové vybavení MeSH
- nanočástice * chemie aplikace a dávkování MeSH
- polyethylenglykoly chemie aplikace a dávkování MeSH
- povidon chemie MeSH
- rozpustnost * MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The advancement of nanotechnology underscores the imperative need for establishing in silico predictive models to assess safety, particularly in the context of chronic respiratory afflictions such as lung fibrosis, a pathogenic transformation that is irreversible. While the compilation of predictive descriptors is pivotal for in silico model development, key features specifically tailored for predicting lung fibrosis remain elusive. This study aimed to uncover the essential predictive descriptors governing nanoparticle-induced pulmonary fibrosis. METHODS: We conducted a comprehensive analysis of the trajectory of metal oxide nanoparticles (MeONPs) within pulmonary systems. Two biological media (simulated lung fluid and phagolysosomal simulated fluid) and two cell lines (macrophages and epithelial cells) were meticulously chosen to scrutinize MeONP behaviors. Their interactions with MeONPs, also referred to as nano-bio interactions, can lead to alterations in the properties of the MeONPs as well as specific cellular responses. Physicochemical properties of MeONPs were assessed in biological media. The impact of MeONPs on cell membranes, lysosomes, mitochondria, and cytoplasmic components was evaluated using fluorescent probes, colorimetric enzyme substrates, and ELISA. The fibrogenic potential of MeONPs in mouse lungs was assessed by examining collagen deposition and growth factor release. Random forest classification was employed for analyzing in chemico, in vitro and in vivo data to identify predictive descriptors. RESULTS: The nano-bio interactions induced diverse changes in the 4 characteristics of MeONPs and had variable effects on the 14 cellular functions, which were quantitatively evaluated in chemico and in vitro. Among these 18 quantitative features, seven features were found to play key roles in predicting the pro-fibrogenic potential of MeONPs. Notably, IL-1β was identified as the most important feature, contributing 27.8% to the model's prediction. Mitochondrial activity (specifically NADH levels) in macrophages followed closely with a contribution of 17.6%. The remaining five key features include TGF-β1 release and NADH levels in epithelial cells, dissolution in lysosomal simulated fluids, zeta potential, and the hydrodynamic size of MeONPs. CONCLUSIONS: The pro-fibrogenic potential of MeONPs can be predicted by combination of key features at nano-bio interfaces, simulating their behavior and interactions within the lung environment. Among the 18 quantitative features, a combination of seven in chemico and in vitro descriptors could be leveraged to predict lung fibrosis in animals. Our findings offer crucial insights for developing in silico predictive models for nano-induced pulmonary fibrosis.
- MeSH
- buňky A549 MeSH
- kovové nanočástice * toxicita chemie MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- plíce účinky léků patologie metabolismus MeSH
- plicní fibróza * chemicky indukované metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment.
- MeSH
- akrylamidy chemie farmakologie aplikace a dávkování MeSH
- antiflogistika farmakologie aplikace a dávkování chemie MeSH
- Aspirin * aplikace a dávkování farmakologie chemie MeSH
- cyklooxygenasy metabolismus MeSH
- inhibitory cyklooxygenasy farmakologie aplikace a dávkování chemie MeSH
- léky s prodlouženým účinkem * MeSH
- mediátory zánětu metabolismus MeSH
- myši MeSH
- nanočástice * chemie MeSH
- nosiče léků chemie MeSH
- polymery * chemie aplikace a dávkování MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Improving the anticancer efficacy of chemotherapeutic drugs and photosensitizers requires innovative multifunctional nanoplatforms. This study introduces a chemo- and phototherapeutic drug delivery system (DDS) based on poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), both PEGylated and non-PEGylated, with a mean size of 200 ± 75 nm. Colchicine (Colch) and purpurin18 (P18) were co-encapsulated into these NPs, and their in vitro drug release profiles were investigated. The anticancer potential of these systems was evaluated across various cell lines (i.e., CaCo-2, PC-3, MCF-7, and MRC-5 cells), demonstrating enhanced NP uptake by cancer cells compared to free drugs. Co-administration of Colch and P18 in 2D and 3D cell line models exhibited a synergistic effect, harnessing both chemotherapeutic and photodynamic effects, leading to higher cancer cell elimination efficacy. This newly developed multifunctional DDS presents a promising platform for combined chemo- and photodynamic therapy in cancer treatment.
- MeSH
- buněčné sféroidy účinky léků MeSH
- fotochemoterapie metody MeSH
- fotosenzibilizující látky aplikace a dávkování chemie farmakologie MeSH
- kolchicin * aplikace a dávkování MeSH
- kopolymer kyseliny glykolové a mléčné * chemie MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory farmakoterapie MeSH
- nanočástice aplikace a dávkování MeSH
- nosiče léků * chemie MeSH
- protinádorové látky aplikace a dávkování chemie farmakologie MeSH
- uvolňování léčiv * MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cévní mozková příhoda, infarkt myokardu a plicní embolie představují významnou zdravotní zátěž pro současnou společnost, přičemž jejich hlavní příčinou jsou krevní sraženiny a poškození vnitřní výstelky cév (endotelu). Přesná a rychlá diagnostika těchto sraženin, zejména určení jejich stáří, je klíčová pro optimální volbu léčebného postupu, jako je trombolýza (farmakologické rozpuštění sraženiny) nebo trombektomie (mechanické odstranění sraženiny). Stávající diagnostické metody však nedosahují požadované úrovně přesnosti a efektivity. Tento článek zkoumá potenciál jodovaných nanočástic (IoNP) na bázi polyjodovaných biodegradabilních polymerů, které mohou cíleně vyhledávat specifické složky, jako je fibrin, a umožnit tak vizualizaci krevních sraženin pomocí rentgenových zobrazovacích metod, jako je počítačová tomografie (CT) nebo skiaskopie. Nanočástice mají schopnost nejen zobrazit sraženiny, ale také odhadnout jejich stáří, což by mohlo výrazně podpořit moderní teranostický přístup, který kombinuje diagnostiku a terapii. Článek také demonstruje možnosti testování farmakokinetiky těchto teranostik pomocí modelového organismu (potkana), využívající metodu laserové ablace s hmotnostní spektrometrií s indukčně vázaným plazmatem. Tento přístup přispívá k lepšímu porozumění biodegradability potenciálních léčiv a představuje klíčový krok v preklinickém hodnocení.
Stroke, myocardial infarction, and pulmonary embolism represent a significant health burden for modern society, with their primary causes being blood clots and damage to the endothelial lining of blood vessels. Accurate and rapid diagnosis of these clots, particularly determining their age, is crucial for optimal treatment selection, such as thrombolysis (pharmacological dissolution of the clot) or thrombectomy (mechanical removal of the clot). However, existing diagnostic methods do not achieve the required levels of accuracy and efficiency. This article explores the potential of iodinated nanoparticles (IoNPs) based on polyiodinated biodegradable polymers, which can selectively target specific components such as fibrin, thereby enabling visualization of blood clots using X-ray imaging techniques like computed tomography (CT) or fluoroscopy. The nanoparticles have the capability not only to visualize clots but also to estimate their age, which could significantly support a modern theranostic approach that combines diagnosis and therapy. The article also demonstrates the possibilities of testing the pharmacokinetics of these theranostics using a model organism (rat), employing the method of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). This approach contributes to a better understanding of the biodegradability of potential therapeutics and represents a key step in preclinical evaluation.
- MeSH
- cévní mozková příhoda diagnostické zobrazování terapie MeSH
- diagnostické zobrazování MeSH
- kontrastní látky MeSH
- lidé MeSH
- nanočástice MeSH
- teranostická nanomedicína * metody MeSH
- trombektomie MeSH
- trombolytická terapie MeSH
- trombóza diagnostické zobrazování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Treating oral diseases remains challenging as API is quickly washed out of the application site by saliva turnover and mouth movements. In situ gels are a class of application forms that present sol-gel transition's ability as a response to stimuli. Their tunable properties are provided using smart polymers responsible for stimuli sensitivity, often providing mucoadhesivity. In this study, antimicrobial in situ gels of thermosensitive and pH-sensitive polymers loaded with silver nanoparticles were prepared and evaluated. The nanoparticles were prepared by green synthesis using Agrimonia eupatoria L. extract. According to the data analysis, the in situ gel with the most promising profile contained 15 % of Pluronic® F-127, 0.25 % of methylcellulose, and 0.1 % of Noveon® AA-1. Pluronic® F-127 and methylcellulose significantly increased the viscosity of in situ gels at 37 °C and shear rates similar to speaking and swallowing. At 20 °C, a behavior close to a Newtonian fluid was observed while being easily injectable (injection force 13.455 ± 1.973 N). The viscosity of the formulation increased with temperature and reached 2962.77 ± 63.37 mPa·s (37 °C). A temperature increase led to increased adhesiveness and rigidity of the formulation. The critical sol-gel transition temperature at physiological pH was 32.65 ± 0.35 °C. 96.77 ± 3.26 % of Ag NPs were released by erosion and dissolution of the gel after 40 min. The determination of MIC showed effect against E. coli and S. aureus (0.0625 mM and 0.5000 mM, respectively). The relative inhibition zone diameter of the in situ gel was 73.32 ± 11.06 % compared to gentamicin sulfate. This work discusses the optimization of the formulation of novel antibacterial in situ gel for oromucosal delivery, analyses the impact of the concentration of excipients on the dependent variables, and suggests appropriate evaluation of the formulation in terms of its indication. This study offers a promising dosage form for local treatment of oral diseases.
The present work reviews the liquid antisolvent crystallization (LASC) to prepare the nanoparticle of pharmaceutical compounds to enhance their solubility, dissolution rate, and bioavailability. The application of ultrasound and additives is discussed to prepare the particles with narrow size distribution. The use of ionic liquid as an alternative to conventional organic solvent is presented. Herbal compounds, also known for low aqueous solubility and limited clinical application, have been crystalized by LASC and discussed here. The particle characteristics such as particle size and particle size distribution are interpreted in terms of supersaturation, nucleation, and growth phenomena. To overcome the disadvantage of batch crystallization, the scientific literature on continuous flow reactors is also reviewed. LASC in a microfluidic device is emerging as a promising technique. The different design of the microfluidic device and their application in LASC are discussed. The combination of the LASC technique with traditional techniques such as high-pressure homogenization and spray drying is presented. A comparison of product characteristics prepared by LASC and the supercritical CO2 antisolvent method is discussed to show that LASC is an attractive and inexpensive alternative for nanoparticle preparation. One of the major strengths of this paper is a discussion on less-explored applications of LASC in pharmaceutical research to attract the attention of future researchers.
A novel ultra-high performance chromatography method with multichannel detection that allows fast, sensitive, and robust analysis of an antifungal drug terbinafine and its three main impurities β-terbinafine, (Z)-terbinafine, and 4-methylterbinafine in just 5.0 min has been developed. Analysis of terbinafine is important in pharmaceutical analysis since it enables the detection of its impurities at very low concentrations. In this study, we focused on the development, optimization, and validation of the UHPLC method as well as its subsequent application in the evaluation of terbinafine and its three main impurities in the dissolution medium to reveal the incorporation of terbinafine in two poly(lactic-co-glycolic acid) (PLGA) carriers and testing of the drug release at pH 5.5. PLGA based drug delivery systems such as solid dispersions, thin films, microparticles, and nanoparticles are new favorable ways of terbinafine administration. PLGA features excellent tissue compatibility, biodegradation, and adjustable drug release profile. Our pre-formulation study indicates that poly(acrylic acid) branched PLGA polyester has more suitable properties than tripentaerythritol branched PLGA polyester. Therefore, the former is likely to enable design of a new drug delivery system for topically applied terbinafine that could facilitate its administration and increase patient compliance.
Long-acting injectable formulations represent a rapidly emerging category of drug delivery systems that offer several advantages compared to orally administered medicines. Rather than having to frequently swallow tablets, the medication is administered to the patient by intramuscular or subcutaneous injection of a nanoparticle suspension that forms a local depot from which the drug is steadily released over a period of several weeks or months. The benefits of this approach include improved medication compliance, reduced fluctuations of drug plasma level, or the suppression of gastrointestinal tract irritation. The mechanism of drug release from injectable depot systems is complex, and there is a lack of models that would enable quantitative parametrisation of the process. In this work, an experimental and computational study of drug release from a long-acting injectable depot system is reported. A population balance model of prodrug dissolution from asuspension with specific particle size distribution has been coupled with the kinetics of prodrug hydrolysis to its parent drug and validated using in vitro experimental data obtained from an accelerated reactive dissolution test. Using the developed model, it is possible to predict the sensitivity of drug release profiles to the initial concentration and particle size distribution of the prodrug suspension, and subsequently simulate various drug dosing scenarios. Parametric analysis of the system has identified the boundaries of reaction- and dissolution-limited drug release regimes, and the conditions for the existence of a quasi-steady state. This knowledge is crucial for the rational design of drug formulations in terms of particle size distribution, concentration and intended duration of drug release.
- MeSH
- antipsychotika * MeSH
- injekce intramuskulární MeSH
- léky s prodlouženým účinkem MeSH
- lidé MeSH
- prekurzory léčiv * MeSH
- rozpustnost MeSH
- suspenze MeSH
- uvolňování léčiv MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
We prepared antibacterial polystyrene nanoparticles (NPs) with natural photosensitizers from chlorophyll (Chl) extract via a simple nanoprecipitation method using the same solvent for dissolution of the polystyrene matrix and extraction of Chls from spinach leaves. A high photo-oxidation and antibacterial effect was demonstrated on Escherichia coli and was based on the photogeneration of singlet oxygen O2(1Δg), which was directly monitored by NIR luminescence measurements and indirectly verified using a chemical trap. The photoactivity of NPs was triggered by visible light, with enhanced red absorption by Chls. To reduce the quenching effect of carotenoids (β-carotene, lutein, etc.) in the Chl extract, diluted and/or preirradiated samples, in which the photo-oxidized carotenoids lose their quenching effect, were used for preparation of the NPs. For enhanced photo-oxidation and antibacterial effects, a sulfonated polystyrene matrix was used for preparation of a stable dispersion of sulfonated NPs, with the quenching effect of carotenoids being suppressed.
- Publikační typ
- časopisecké články MeSH
