Prediction of poly(lactic-co-glycolic acid) (PLGA) micro- and nanoparticles' dissolution rates plays a significant role in pharmaceutical and medical industries. The prediction of PLGA dissolution rate is crucial for drug manufacturing. Therefore, a model that predicts the PLGA dissolution rate could be beneficial. PLGA dissolution is influenced by numerous factors (features), and counting the known features leads to a dataset with 300 features. This large number of features and high redundancy within the dataset makes the prediction task very difficult and inaccurate. In this study, dimensionality reduction techniques were applied in order to simplify the task and eliminate irrelevant and redundant features. A heterogeneous pool of several regression algorithms were independently tested and evaluated. In addition, several ensemble methods were tested in order to improve the accuracy of prediction. The empirical results revealed that the proposed evolutionary weighted ensemble method offered the lowest margin of error and significantly outperformed the individual algorithms and the other ensemble techniques.

• MeSH
• algoritmy MeSH
• kyselina mléčná chemie   MeSH
• kyselina polyglykolová chemie   MeSH
• mikrosféry MeSH
• nanočástice chemie   MeSH
• rozpustnost MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Flow-through cell dissolution method was implemented in pharmacopoeias in 1990 and since that time its usage significantly increased. It is employed in oral dosage forms with controlled drug release to measure dissolved drug amount within particular time intervals and to characterize pure drug properties (apparent dissolution). Modified flow-through cell is used to determine the drug dissolution from lipophilic dosage forms such as suppositories and soft capsules. Recently, few modifications of this method were published in order to provide drug release studies from parenteral controlled release products and inhalation dosage forms. Review article is presenting last innovations in this area, i.e. new adjustment and arrangement of flow-through cell method, to assess drug release from implants, micro- and nanoparticulate systems, stents and inhalation medicaments in the way more corresponding to in-vivo conditions.

• Klíčová slova
• in vitro - in vivo,
• MeSH
• aplikace inhalační MeSH
• biologická dostupnost MeSH
• elektrochemické techniky * metody   přístrojové vybavení   využití   MeSH
• farmaceutická technologie normy   MeSH
• hodnocení léčiv * MeSH
• lékové formy normy   MeSH
• lékové transportní systémy * MeSH
• lidé MeSH
• nanočástice MeSH
• protézy a implantáty MeSH
• referenční knihy normy   MeSH
• rozpustnost * MeSH
• stenty MeSH
• Check Tag
• lidé MeSH

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

The rapid dissolution of copper oxide (CuO) nanoparticles (NPs) with release of ions is thought to be one of the main factors modulating their toxicity. Here we assessed the cytotoxicity of a panel of CuO NPs (12 nm ± 4 nm) with different surface modifications, i.e., anionic sodium citrate (CIT) and sodium ascorbate (ASC), neutral polyvinylpyrrolidone (PVP), and cationic polyethylenimine (PEI), versus the pristine (uncoated) NPs, using a murine macrophage cell line (RAW264.7). Cytotoxicity, reactive oxygen species (ROS) production, and cellular uptake were assessed. The cytotoxicity results were analyzed by the benchmark dose (BMD) method and the NPs were ranked based on BMD20values. The PEI-coated NPs were found to be the most cytotoxic. Despite the different properties of the coating agents, NP dissolution in cell medium was only marginally affected by surface modification. Furthermore, CuCl2(used as an ion control) elicited significantly less cytotoxicity when compared to the CuO NPs. We also observed that the antioxidant, N-acetylcysteine, failed to protect against the cytotoxicity of the uncoated CuO NPs. Indeed, the toxicity of the surface-modified CuO NPs was not directly linked to particle dissolution and subsequent Cu burden in cells, nor to cellular ROS production, although CuO-ASC NPs, which were found to be the least cytotoxic, yielded lower levels of ROS in comparison to pristine NPs. Hierarchical cluster analysis suggested, instead, that the toxicity in the current in vitro model could be explained by synergistic interactions between the NPs, their dissolution, and the toxicity of the coating agents.

• MeSH
• antioxidancia MeSH
• buněčná smrt účinky léků   MeSH
• buněčné linie MeSH
• kovové nanočástice chemie   toxicita   MeSH
• makrofágy metabolismus   MeSH
• měď chemie   farmakokinetika   toxicita   MeSH
• myši MeSH
• povrchové vlastnosti MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• rozpustnost MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

We have developed a biodegradable, biocompatible system for the delivery of the antituberculotic antibiotic rifampicin with a built-in drug release and nanoparticle degradation fluorescence sensor. Polymer nanoparticles based on poly(ethylene oxide) monomethyl ether-block-poly(ε-caprolactone) were noncovalently loaded with rifampicin, a combination that, to best of our knowledge, was not previously described in the literature, which showed significant benefits. The nanoparticles contain a Förster resonance energy transfer (FRET) system that allows real-time assessment of drug release not only in vitro, but also in living macrophages where the mycobacteria typically reside as hard-to-kill intracellular parasites. The fluorophore also enables in situ monitoring of the enzymatic nanoparticle degradation in the macrophages. We show that the nanoparticles are efficiently taken up by macrophages, where they are very quickly associated with the lysosomal compartment. After drug release, the nanoparticles in the cmacrophages are enzymatically degraded, with half-life 88±11 min.

• MeSH
• antituberkulotika aplikace a dávkování   MeSH
• biokompatibilní materiály chemie   MeSH
• lékové transportní systémy * MeSH
• makrofágy účinky léků   metabolismus   MeSH
• myši MeSH
• nanočástice chemie   MeSH
• polyestery chemie   MeSH
• polyethylenglykoly chemie   MeSH
• RAW 264.7 buňky MeSH
• rezonanční přenos fluorescenční energie MeSH
• rifampin aplikace a dávkování   MeSH
• uvolňování léčiv * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

Targeted delivery combined with controlled drug release has a pivotal role in the future of personalized medicine. This review covers the principles, advantages, and drawbacks of passive and active targeting based on various polymer and magnetic iron oxide nanoparticle carriers with drug attached by both covalent and noncovalent pathways. Attention is devoted to the tailored conjugation of targeting ligands (e.g., enzymes, antibodies, peptides) to drug carrier systems. Similarly, the approaches toward controlled drug release are discussed. Various polymer-drug conjugates based, for example, on polyethylene glycol (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), polymeric micelles, and nanoparticle carriers are explored with respect to absorption, distribution, metabolism, and excretion (ADME scheme) of administrated drug. Design and structure of superparamagnetic iron oxide nanoparticles (SPION) and condensed magnetic clusters are classified according to the mechanism of noncovalent drug loading involving hydrophobic and electrostatic interactions, coordination chemistry, and encapsulation in porous materials. Principles of covalent conjugation of drugs with SPIONs including thermo- and pH-degradable bonds, amide linkage, redox-cleavable bonds, and enzymatically-cleavable bonds are also thoroughly described. Finally, results of clinical trials obtained with polymeric and magnetic carriers are analyzed highlighting the potential advantages and future directions in targeted anticancer therapy.

• MeSH
• koncentrace vodíkových iontů MeSH
• lékové transportní systémy * MeSH
• ligandy MeSH
• magnetické nanočástice chemie   MeSH
• nosiče léků chemie   MeSH
• polymery chemie   MeSH
• poréznost MeSH
• povrchové vlastnosti MeSH
• uvolňování léčiv * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The present work highlights recent achievements in development of nanostructured dispersions and biocolloids for drug delivery applications. We emphasize the key role of biological small-angle X-ray scattering (BioSAXS) investigations for the nanomedicine design. A focus is given on controlled encapsulation of small molecular weight phytochemical drugs in lipid-based nanocarriers as well as on encapsulation of macromolecular siRNA, plasmid DNA, peptide and protein pharmaceuticals in nanostructured nanoparticles that may provide efficient intracellular delivery and triggered drug release. Selected examples of utilisation of the BioSAXS method for characterization of various types of liquid crystalline nanoorganizations (liposome, spongosome, cubosome, hexosome, and nanostructured lipid carriers) are discussed in view of the successful encapsulation and protection of phytochemicals and therapeutic biomolecules in the hydrophobic or the hydrophilic compartments of the nanocarriers. We conclude that the structural design of the nanoparticulate carriers is of crucial importance for the therapeutic outcome and the triggered drug release from biocolloids.

• MeSH
• difrakce rentgenového záření MeSH
• fytonutrienty chemie   farmakologie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• koloidy MeSH
• lidé MeSH
• malá interferující RNA genetika   metabolismus   MeSH
• maloúhlový rozptyl MeSH
• nanočástice chemie   MeSH
• nosiče léků * MeSH
• peptidy chemie   metabolismus   MeSH
• plazmidy chemie   metabolismus   MeSH
• příprava léků metody   MeSH
• protinádorové látky chemie   farmakologie   MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The alkaline milieu of chronic wounds severely impairs the therapeutic effect of antibiotics, such as rifampicin; as such, the development of new drugs, or the smart delivery of existing drugs, is required. Herein, two innovative polyelectrolyte nanoparticles (PENs), composed of an amphiphilic chitosan core and a polycationic shell, were synthesized at alkaline pH, and in vitro performances were assessed by 1H NMR, elemental analysis, FT-IR, XRD, DSC, DLS, SEM, TEM, UV/Vis spectrophotometry, and HPLC. According to the results, the nanostructures exhibited different morphologies but similar physicochemical properties and release profiles. It was also hypothesized that the simultaneous use of the nanosystem and an antioxidant could be therapeutically beneficial. Therefore, the simultaneous effects of ascorbic acid and PENs were evaluated on the release profile and degradation of rifampicin, in which the results confirmed their synergistic protective effect at pH 8.5, as opposed to pH 7.4. Overall, this study highlighted the benefits of nanoparticulate development in the presence of antioxidants, at alkaline pH, as an efficient approach for decreasing rifampicin degradation.

• MeSH
• diferenciální skenovací kalorimetrie MeSH
• difrakce rentgenového záření MeSH
• koncentrace vodíkových iontů MeSH
• lékové transportní systémy * MeSH
• nanočástice chemie   ultrastruktura   MeSH
• polyelektrolyty chemie   MeSH
• protonová magnetická rezonanční spektroskopie MeSH
• rifampin farmakologie   MeSH
• síran dextranu chemie   MeSH
• spektrofotometrie ultrafialová MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• statická elektřina MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH

In solid tumors, hypoxia (lack of oxygen) is developed, which leads to the development of resistance of tumor cells to chemotherapy and radiotherapy through various mechanisms. Nevertheless, hypoxic cells are particularly vulnerable when glycolysis is inhibited. For this reason, in this study, the development of magnetically targetable nanocarriers of the sodium-glucose transporter protein (SGLT2) inhibitor dapagliflozin (DAPA) was developed for the selective delivery of DAPA in tumors. This nanomedicine in combination with radiotherapy or chemotherapy should be useful for effective treatment of hypoxic tumors. The magnetic nanoparticles consisted of a magnetic iron oxide core and a poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate) (PMAA-g-PEGMA) polymeric shell. The drug (dapagliflozin) molecules were conjugated on the surface of these nanoparticles via in vivo hydrolysable ester bonds. The nanoparticles had an average size of ~ 70 nm and exhibited a DAPA loading capacity 10.75% (w/w) for a theoretical loading 21.68% (w/w). The magnetic responsiveness of the nanoparticles was confirmed with magnetophoresis experiments. The dapagliflozin-loaded magnetic nanoparticles exhibited excellent colloidal stability in aqueous and biological media. Minimal (less than 15% in 24 h) drug release from the nanoparticles occurred in physiological pH 7.4; however, drug release was significantly accelerated in pH 5.5. Drug release was also accelerated (triggered) under the influence of an alternating magnetic field. The DAPA-loaded nanoparticles exhibited higher in vitro anticancer activity (cytotoxicity) against A549 human lung cancer cells than free DAPA. The application of an external magnetic field gradient increased the uptake of nanoparticles by cells, leading to increased cytotoxicity. The results justify further in vivo studies of the suitability of DAPA-loaded magnetic nanoparticles for the treatment of hypoxic tumors.

• MeSH
• benzhydrylové sloučeniny aplikace a dávkování   chemie   MeSH
• buňky A549 MeSH
• glifloziny MeSH
• glukosidy aplikace a dávkování   chemie   MeSH
• lékové transportní systémy metody   MeSH
• lidé MeSH
• magnetické nanočástice aplikace a dávkování   chemie   MeSH
• nádorová hypoxie účinky léků   fyziologie   MeSH
• nádorové buněčné linie MeSH
• nanomedicína metody   MeSH
• nosiče léků aplikace a dávkování   chemie   MeSH
• transportér 2 pro sodík a glukózu MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH