Micro- and nanostructures prepared from biodegradable homopolymers and amphiphilic block copolymers (AmBCs) have found application as drug-delivery systems (DDSs). The ability to accumulate a drug is a very important parameter characterizing a given DDS. This work focuses on the impact of DDS size, the packing of polymer chains in the DDS, and drug - polymer matrix compatibility on the hydrophobic drug - loading capacity (DLC) of nano/microcarriers prepared from a biodegradable polymer or its copolymer. Using experimental measurements in combination with atomistic molecular dynamics simulations, an analysis of curcumin encapsulation in microspheres (MSs) from polylactide (PLA) homopolymer and nanoparticles (NPs) from PLA-block-poly(2-methacryloyloxyethylphosphorylcholine) AmBC was performed. The results show that curcumin has good affinity for the PLA matrix due to its hydrophobic nature. However, the DLC value is limited by the fact that curcumin only accumulates in the peripheral part of these structures. Such uneven drug distribution in the PLA matrix results from the non-homogeneous density of MSs (non-uniform packing of the polymer chains in the coil). The results also indicate that the MSs can retain a greater amount of hydrophobic drug compared to the NPs, which is associated with the formation of drug aggregates inside the PLA microparticles.

• MeSH
• léčivé přípravky * MeSH
• nanočástice * MeSH
• nosiče léků MeSH
• polyestery MeSH
• polyethylenglykoly MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH

The sorption of poorly aqueous soluble active pharmaceutical ingredients (API) to mesoporous silica carriers is an increasingly common formulation strategy for dissolution rate enhancement for this challenging group of substances. However, the success of this approach for a particular API depends on an array of factors including the properties of the porous carrier, the loading method, or the attempted mass fraction of the API. At present, there is no established methodology for the rational selection of these parameters. In the present work, we report a systematic comparison of four well-characterised silica carriers and seven APIs loaded by the same solvent evaporation method. In each case, we find the maximum amorphization capacity by x-ray powder diffraction analysis and measure the in vitro drug release kinetics. For a selected case, we also demonstrate the potential for bioavailability enhancement by a permeation essay.

• MeSH
• kinetika MeSH
• nosiče léků * MeSH
• oxid křemičitý * MeSH
• poréznost MeSH
• rozpouštědla MeSH
• rozpustnost MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH

Despite the increasing interest in pharmaceutical use of mesoporous silica, there is still only limited knowledge on mechanisms of pore loading and subsequent drug desorption and release. Hence the aim of this work was to address the mechanistic aspects of drug loading into the mesoporous silica pores and to minimise the risk of pore clogging. Hydrophilic solvents (polysorbate 20 and polyethylene glycol 200) with high dissolving capacity for the model drug celecoxib were studied for their surface tension as well as dynamic viscosity by considering hydration. As an innovation in liquisolid systems preparation, a rather simple drug loading method on a mesoporous carrier was introduced by using semi-volatile solvent mixtures. Fast liquid loading into the pores was achieved due to the lowered viscosity and surface tension of the whole solvent system. Drug release kinetics suggested that lipid-based formulations belonging to class IV of Lipid Formulation Classification System may exhibit a lower risk of incomplete desorption from a carrier. The utilisation of volatile solvents during preparation had no negative impact on the liquisolid systems' dissolution behaviour. All prepared formulations showed similar significantly faster dissolution profiles compared to the physical mixture. The novel approach has potential to promote liquisolid applications in pharmaceutics.

• MeSH
• diferenciální skenovací kalorimetrie metody   MeSH
• farmaceutická chemie metody   MeSH
• farmaceutická technologie metody   MeSH
• hydrofobní a hydrofilní interakce MeSH
• kinetika MeSH
• léčivé přípravky chemie   MeSH
• lipidy chemie   MeSH
• nosiče léků chemie   MeSH
• oxid křemičitý chemie   MeSH
• polysorbáty chemie   MeSH
• propylenglykol chemie   MeSH
• rozpouštědla chemie   MeSH
• rozpustnost účinky léků   MeSH
• tablety chemie   MeSH
• Publikační typ
• časopisecké články MeSH

Polymeric micelles are attractive drug delivery systems for intravenously administered nonpolar drugs. Although physical parameters like size, shape and loading capacity are considered as the most important for their efficiency, here we demonstrate that the effects of serum protein interaction and characteristics of loaded compound cannot be neglected during the micelle development and design of experimental set up. Polymeric micelles prepared from amphiphilic hyaluronic acid grafted with short (hexanoic) and long fatty acids (oleic) were tested after loading with two different hydrophobic models, Nile red and curcumin. The composition of micelles affected mainly the loading capacity. Both encapsulated compounds behaved differently in the in vitro cell uptake, which was also influenced by serum concentration, where serum albumin was found to be the primary destabilizing component. This destabilization was found to be influenced by polymeric micelle concentration. Thus, the chemical structure of micelle, the properties of non-covalently loaded substance and serum albumin/polymeric micelle ratio modulate the in vitro intracellular uptake of drugs loaded in nanocarriers.

• MeSH
• buňky HT-29 MeSH
• HCT116 buňky MeSH
• intracelulární tekutina účinky léků   metabolismus   MeSH
• kyselina hyaluronová aplikace a dávkování   metabolismus   MeSH
• lékové transportní systémy metody   MeSH
• lidé MeSH
• micely * MeSH
• nosiče léků aplikace a dávkování   metabolismus   MeSH
• polymery aplikace a dávkování   metabolismus   MeSH
• sérový albumin aplikace a dávkování   metabolismus   MeSH
• vazba proteinů fyziologie   MeSH
• viabilita buněk účinky léků   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Sublingual administration of active pharmaceutical substances is in principle favourable for rapid onset of drug action, ready accessibility and avoidance of first pass metabolism. This administration could prove very useful in the treatment of migraines, thus two frequently used drugs were selected for our study. Sumatriptan succinate, naproxen, and its salt as well as combinations of these were incorporated into nanofibrous membranes via the electrospinning process. DSC measurements proved that the resulted membranes contained non-crystalline drug forms. SEM imaging approved good homogeneity of diameter and shape of the membrane nanofibres. The nanofibrous membranes always showed the rapid and mutually independent release of the tested drugs. The drugs exhibited very high differences in sublingual permeation rates in vitro, but the rates of both substances were increased several times using nanofibrous membranes as the drug carrier in comparison to drug solutions. The released drugs subsequently permeated through sublingual mucosa preferentially as non-ionized moieties. The prepared nanofibrous membranes proved very flexible and mechanically resistant. With their drug load capacity of up to 40% of membrane mass, they could be very advantageous for the formulation of sublingual drug delivery systems.

• MeSH
• antiflogistika nesteroidní aplikace a dávkování   chemie   MeSH
• aplikace sublinguální MeSH
• lékové transportní systémy * MeSH
• nanovlákna chemie   MeSH
• naproxen aplikace a dávkování   chemie   MeSH
• prasata MeSH
• sumatriptan aplikace a dávkování   chemie   MeSH
• techniky in vitro MeSH
• ústní sliznice metabolismus   MeSH
• vazokonstriktory aplikace a dávkování   chemie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Background: The research is aimed at exploring the potential of marigold petal tea (MPT), rich in polyphenol contents, against oxidative stress and obesity in a rat model following a high-fat-sugar diet (HFSD). Methods: The MPT was prepared through the customary method of decoction and was subjected to analysis for its polyphenol composition using reversed-phase high-performance liquid chromatography (RP-HPLC). Two specific doses of MPT, namely, 250 and 500 mg/kg body weight (BW), were chosen for the study-referred to as MPT-250 and MPT-500, respectively. Result: The main phenolic acids and flavonoids identified in MPT, with concentrations exceeding 10 mg/100 mL of tea, included catechin, rutin, salicylic acid, gallic acid, sinapic acid, chlorogenic acid, cinnamic acid, and ellagic acid. The total phenolic (TP) and total flavonoid (TF) contents in MPT were measured to be 5.53 and 7.73 mg/g, respectively. Additionally, MPT demonstrated a 57.2% scavenging capacity with 2,2-diphenyl-1-picrylhydrazyl radical. Notably, the administration of a higher dose (MPT-500) showed a significant reduction in body mass index (BMI) and a 51.24% reduction in the rate of increase in BW compared to the HFSD group. The findings indicated that all the treatment groups, that is, orlistat treatment (OT), MPT-250, and MPT-500 groups, experienced reduced levels of serum total cholesterol (TC), triglyceride (TG), and markers of lipoproteins in contrast to the HFSD group. Moreover, MPT helped restore the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), thereby demonstrating its potential in combating oxidative stress. The MPT-500 group also displayed decreased liver and kidney weights and an improved atherogenic index when compared to the HFSD group. Conclusion: The results clearly indicate that a high dosage of MPT showed antiobesity activity which was comparable to the same effects produced by the conventional drug orlistat.

• MeSH
• antioxidancia * farmakologie   MeSH
• biologické markery * krev   MeSH
• dieta s vysokým obsahem tuků * MeSH
• hmotnostní úbytek účinky léků   MeSH
• játra účinky léků   metabolismus   MeSH
• krysa rodu rattus MeSH
• látky proti obezitě * farmakologie   MeSH
• modely nemocí na zvířatech * MeSH
• obezita * farmakoterapie   metabolismus   MeSH
• oxidační stres * účinky léků   MeSH
• polyfenoly * farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• rostlinné extrakty farmakologie   izolace a purifikace   MeSH
• sacharidová dieta škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Ferritin, a naturally occurring iron storage protein, has gained significant attention as a drug delivery platform due to its inherent biocompatibility and capacity to encapsulate therapeutic agents. In this study, we successfully genetically engineered human H ferritin by incorporating 4 or 6 tryptophan residues per subunit, strategically oriented towards the inner cavity of the nanoparticle. This modification aimed to enhance the encapsulation of hydrophobic drugs into the ferritin cage. Comprehensive characterization of the mutants revealed that only the variant carrying four tryptophan substitutions per subunit retained the ability to disassemble and reassemble properly. As a proof of concept, we evaluated the loading capacity of this mutant with ellipticine, a natural hydrophobic indole alkaloid with multimodal anticancer activity. Our data demonstrated that this specific mutant exhibited significantly higher efficiency in loading ellipticine compared to human H ferritin. Furthermore, to evaluate the versatility of this hydrophobicity-enhanced ferritin nanoparticle as a drug carrier, we conducted a comparative study by also encapsulating doxorubicin, a commonly used anticancer drug. Subsequently, we tested both ellipticine and doxorubicin-loaded nanoparticles on a promyelocytic leukemia cell line, demonstrating efficient uptake by these cells and resulting in the expected cytotoxic effect.

• MeSH
• apoferritiny genetika   MeSH
• doxorubicin farmakologie   chemie   MeSH
• elipticiny * MeSH
• ferritiny genetika   chemie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• protinádorové látky * farmakologie   chemie   MeSH
• tryptofan MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Although the systemic administration of terbinafine is quite well tolerated, topical treatment of the local infections is often preferred. New formulation strategies in topical antifungal therapy represent the polymeric nanoparticles (NPs). We successfully employed the originally synthesized PLGA derivatives of branched architectures of various molar masses, branching ratio, and high number of terminal hydroxyl or carboxyl groups for compounding of terbinafine loaded nanoparticles by nanoprecipitation method. Employing the polymers with tailored properties allowed us to formulate the NPs with desired particle size, loading capacity for drug, mucoadhesive properties, and drug release profile. The hydrophobicity and the polyester concentration revealed the main impact on the NPs size ranging from 100 to 600 nm. The stability of the nanosuspension is demonstrated by zeta potential >25 mV, and polydispersity index values <0.2. We used terbinafine in its less dissolved form of the base to increase the drug loading and delay the release. Cationic surfactant as stabilizer give the NPs high positive surface charge enhancing the adhesion to the mucosal surfaces. All formulations provided prolonged sustained release of terbinafine for several days. Antimicrobial potential has been proven by agar-well diffusion method.

• MeSH
• antifungální látky aplikace a dávkování   chemie   MeSH
• aplikace lokální MeSH
• hydrofobní a hydrofilní interakce MeSH
• kationty MeSH
• kopolymer kyseliny glykolové a mléčné chemie   MeSH
• nanočástice chemie   MeSH
• nosiče léků chemie   MeSH
• povrchově aktivní látky chemie   MeSH
• povrchové vlastnosti MeSH
• příprava léků metody   MeSH
• rozpustnost MeSH
• terbinafin aplikace a dávkování   chemie   MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• viskozita MeSH
• Publikační typ
• časopisecké články MeSH

Modern drugs with low bioavailability (such as hypolipidemics, anti-inflammatory drugs, diuretics) present, due to their poor water solubility a significant problem in the formulation of solid dosage forms intended for systemic absorption of the active substance. Several methods have been described for improving solubility and hence bioavailability of the mentioned drugs. One of the most promising techniques is the incorporation of active substance in liquid-solid systems. The systems are based on the conversion of a liquid drug to a free-flowing compressible dry powder, by sorption on suitable excipients – porous carriers (alumsilicates, microcrystalline cellulose), coated subsequently with a material of high absorption capacity (SiO2). Liquid-solid systems exhibit some advantages including low production costs, simple processing and enhanced drug release. The main benefit is high bioavailability of the liquid drug, caused by the large surface area available for absorption without previous dissolution of active substance. The review clarifies specific aspects associated with the formulation of liquid-solid systems – excipients and their properties (surface area, adsorption capacity), methods of preparation, process variables (solubility, liquid loading) and evaluation of the dosage form.

• MeSH
• absorpce MeSH
• antiflogistika aplikace a dávkování   farmakokinetika   MeSH
• biologická dostupnost * MeSH
• chemické jevy MeSH
• diuretika aplikace a dávkování   farmakokinetika   MeSH
• farmaceutická technologie MeSH
• hypolipidemika aplikace a dávkování   farmakokinetika   MeSH
• lékové formy MeSH
• lékové transportní systémy * MeSH
• lidé MeSH
• methylcelulosa MeSH
• nosiče léků MeSH
• polyethylenglykoly MeSH
• povrchově aktivní látky MeSH
• racionální návrh léčiv * MeSH
• rozpustnost MeSH
• tablety MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem 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