RESUMO
New insights into the unique biochemical properties of riboflavin (Rf), also known as vitamin B2, are leading to the development of its use not only as a vitamin supplement but also as a potential anti-inflammatory, immunomodulatory, antioxidant, anticancer, and antiviral agent, where it may play a role as an inhibitor of viral proteinases. At the same time, the comparison of the pharmacoactivity of Rf with its known metabolites, namely, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), is very complicated due to its poor water solubility: 0.1-0.3 g/L versus 67 g/L for FMN and 50 g/L for FAD, which is the limiting factor for its administration in clinical practice. In this study, we report the recrystallization procedure of the type A Rf crystals into the slightly hydrophobic type B/C and a new hydrophilic crystal form that has been termed the P type. Our method of Rf crystal modification based on recrystallization from dilute alkaline solution provides an unprecedented extremely high water solubility of Rf, reaching 23.5 g/L. A comprehensive study of the physicochemical properties of type P riboflavin showed increased photodynamic therapeutic activity compared to the known types A and B/C against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Salmonella typhimurium. Importantly, our work not only demonstrates a simple and inexpensive method for the synthesis of riboflavin with high solubility, which should lead to increased bioactivity, but also opens up opportunities for improving both known and new therapeutic applications of vitamin B2.
Assuntos
Mononucleotídeo de Flavina , Flavina-Adenina Dinucleotídeo , Flavina-Adenina Dinucleotídeo/metabolismo , Solubilidade , Riboflavina , Escherichia coli/metabolismo , ÁguaRESUMO
Capsules with shells based on nanoparticles of different nature co-assembled at the interface of liquid phases of emulsion are promising carriers of lipophilic drugs. To obtain such capsules, theoretically using the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory and experimentally using dynamic light-scattering (DLS) and transmission electron microscopy (TEM) methods, the interaction of like-charged silica nanoparticles and detonation nanodiamonds in an aqueous solution was studied and their ratios selected for the formation of submicron-sized colloidosomes. The resulting colloidosomes were modified with additional layers of nanoparticles and polyelectrolytes, applying LbL technology. As a model anti-cancer drug, thymoquinone was loaded into the developed capsules, demonstrating a significant delay of the release as a result of colloidosome surface modification. Fluorescence flow cytometry and confocal laser scanning microscopy showed efficient internalization of the capsules by MCF7 cancer cells. The obtained results demonstrated a high potential for nanomedicine application in the field of the drug-delivery system development.
RESUMO
Nanosystems for targeted delivery and remote-controlled release of therapeutic agents has become a top priority in pharmaceutical science and drug development in recent decades. Application of a low frequency magnetic field (LFMF) as an external stimulus opens up opportunities to trigger release of the encapsulated bioactive substances with high locality and penetration ability without heating of biological tissue in vivo. Therefore, the development of novel microencapsulated drug formulations sensitive to LFMF is of paramount importance. Here, we report the result of LFMF-triggered release of the fluorescently labeled dextran from polyelectrolyte microcapsules modified with magnetic iron oxide nanoparticles. Polyelectrolyte microcapsules were obtained by a method of sequential deposition of oppositely charged poly(allylamine hydrochloride) (PAH) and poly(sodium 4-styrenesulfonate) (PSS) on the surface of colloidal vaterite particles. The synthesized single domain maghemite nanoparticles integrated into the polymer multilayers serve as magneto-mechanical actuators. We report the first systematic study of the effect of magnetic field with different frequencies on the permeability of the microcapsules. The in situ measurements of the optical density curves upon the 100 mT LFMF treatment were carried out for a range of frequencies from 30 to 150 Hz. Such fields do not cause any considerable heating of the magnetic nanoparticles but promote their rotating-oscillating mechanical motion that produces mechanical forces and deformations of the adjacent materials. We observed the changes in release of the encapsulated TRITC-dextran molecules from the PAH/PSS microcapsules upon application of the 50 Hz alternating magnetic field. The obtained results open new horizons for the design of polymer systems for triggered drug release without dangerous heating and overheating of tissues.
RESUMO
The photocatalytic degradation of organic molecules is one of the effective ways for water purification. At this point, photocatalytic microreactor systems seem to be promising to enhance the versatility of the photoassisted degradation approach. Herein, we propose photoresponsive microcapsules prepared via layer-by-layer assembly of polyelectrolytes on the novel CaCO3/TiO2 composite template cores. The preparation of CaCO3/TiO2 composite particles is challenging because of the poor compatibility of TiO2 and CaCO3 in an aqueous medium. To prepare stable CaCO3/TiO2 composites, TiO2 nanoparticles were loaded into mesoporous CaCO3 microparticles with a freezing-induced loading technique. The inclusion of TiO2 nanoparticles into CaCO3 templates was evaluated with scanning electron microscopy and elemental analysis with respect to their type, concentration, and number of loading iterations. Upon polyelectrolyte shell assembly, the CaCO3 matrix was dissolved, resulting in microreactor capsules loaded with TiO2 nanoparticles. The photoresponsive properties of the resulted capsules were tested by photoinduced degradation of the low-molecule dye rhodamine B in aqueous solution and fluorescently labeled polymer molecules absorbed on the capsule surface under UV light. The exposure of the capsules to UV light resulted in a pronounced degradation of rhodamine B in capsule microvolume and fluorescent molecules on the capsule surface. Finally, the versatility of preparation of multifunctional photocatalytic and magnetically responsive capsules was demonstrated by iterative freezing-induced loading of TiO2 and magnetite Fe3O4 nanoparticles into CaCO3 templates.
RESUMO
Submicrocapsules were prepared from diethylaminoethyl dextran (DEAE-D), xanthan gum (XG) and bovine serum albumin (BSA) on oil cores by ultrasonic treatment. These capsules were modified with poly-L-lysine (PLL) via electrostatic adsorption. The behavior of the capsules was investigated at an air-water interface after their introduction into an aqueous subphase. The interaction of the capsules with 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) monolayer formed on the water surface (model cellular membrane) was studied both upon their introduction under the condensed monolayer and with the use of a dilute colloidal solution of the capsules as a subphase. Biodegradation of the proteinaceous capsules with subsequent oil-core release was demonstrated by influence of pronase. The Langmuir lipid monolayer was found to be a good model for investigation of drug release from the capsules in the presence of the cellular membrane.
Assuntos
Cápsulas/química , Membrana Celular/química , Bicamadas Lipídicas/química , Lipídeos/química , Polímeros/química , Adsorção , Animais , Cápsulas/metabolismo , Bovinos , Membrana Celular/metabolismo , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Interações Hidrofóbicas e Hidrofílicas , Bicamadas Lipídicas/metabolismo , Polímeros/metabolismo , Soroalbumina Bovina/química , Eletricidade Estática , Propriedades de Superfície , Água/químicaRESUMO
Aiming to explore elevated temperatures as a tool for miniaturization of biodegradable polymer multilayer capsules, assembled on spherical vaterite micron- and submicron-sized particles, we subject the shells composed of dextran sulfate (DS) and poly-L-arginine (Parg) to a heat treatment. Changes of the capsule size are studied at various temperatures and ionic strengths of the continuous phase. Unlike some synthetic polymer multilayer shells (their response to heat treatment depends on the number of layers and their arrangement), the biodegradable Parg/DS capsules exhibit size reduction and profound compaction regardless of their initial size, number of polymer layers and polymer layer sequence. The capsule response to heat is stable at ionic strengths of the continuous phase not exceeding 0.1â¯M NaCl.
Assuntos
Carbonato de Cálcio/química , Temperatura Alta , Peptídeos/química , Cápsulas/química , Sulfato de Dextrana/química , Eletrólitos/química , Oxirredução , Tamanho da Partícula , Porosidade , Propriedades de SuperfícieRESUMO
Among the polymorph modifications of calcium carbonate, the metastable vaterite is the most practically important. Vaterite particles are applied in regenerative medicine, drug delivery and a broad range of personal care products. This manuscript scopes to review the mechanism of the calcium carbonate crystal growth highlighting the factors stabilizing the vaterite polymorph in the most cost efficient synthesis routine. The size of vaterite particles is a crucial parameter for practical applications. The options for tuning the particle size are also discussed.