Regime shift in microalgal dynamics: Impact of water level changes on planktonic and benthic algal biomass.

Whole-lake microalgal biomass surveys were carried out in Lake Balaton to investigate the seasonal, spatial, and temporal changes of benthic algae, as well as to identify the drivers of the phytobenthos. Phytobenthos was controlled mainly by light: the highest benthic algal biomass was in the shallow littoral region characterized by large grain size (sand) with good light availability but lower nutrient content in the sediment. During the investigated period, phytoplankton biomass showed a significant decrease in almost the entire lake. At the same time, the biomass of benthic algae increased significantly in the eastern areas, increasing the contribution of total lake microalgae biomass (from 20 % to 27 %). Benthic algal biomass increase can be explained by the better light supply, owing to the artificially maintained high water level which greatly mitigates water mixing. The decrease in planktonic algal biomass could be attributed to increased zooplankton grazing, which is otherwise negatively affected by mixing. As a result of the high water level, the trophic structure of the lake has been rearranged in recent decades with a shift from the planktonic life form to the benthic one while the nutrient supply has largely remained unchanged.

Topical Formulation of Nano Spray-Dried Levocetirizine Dihydrochloride against Allergic Edema.

Levocetirizine dihydrochloride active ingredient was microencapsulated using nano spray-drying technology for preparing microparticles containing topical gel against edema. Hydroxyl propyl methyl cellulose (HPMC) was used as a carrier polymer during spray drying. The active ingredient content of the nano spray-dried products was 52.81% (w/w) and 51.33% (w/w) for ex vivo and in vivo experiments, respectively, and the average particle size was 2.6 µm. X-ray diffraction analysis indicated an amorphous state of the active ingredient embedded in the amorphous matrix of the polymer. Dermal oil gels composed of Miglyol 812 gelated by Dermofeel viscolid included 5% (w/w) (for ex vivo) and 10% (w/w) (for in vivo) active ingredient without or with 0.05% (w/w) menthol penetration enhancer. Qualitative ex vivo penetration studies using a confocal Raman microscopic correlation mapping were executed on human abdominal skin. The results showed that the active ingredient was enriched in the epidermis and upper dermis layer of the skin using oleogel loaded with the nano spray-dried drug-HPMC composite. Menthol addition to the oleogel resulted in the concentration of levocetirizine in the dermis. In vivo tests were performed on a mouse model of croton oil-induced ear edema. Negative control and Fenistil-treated groups were compared using the prepared oil gels with and without menthol. Without penetration enhancer, 20 µL of our oil gel loaded with nano spray-dried levocetirizine dihydrochloride composite showed similar effectiveness to the same volume of Fenistil gel, while 5 µL menthol containing sample was sufficient to eliminate the skin irritation similarly to 20 µL Fenistil.

Halochromic Behavior and Anticancer Effect of New Synthetic Anthocyanidins Complexed with ß-Cyclodextrin Derivatives.

Anthocyanidins, the aglycons of anthocyanins, are known, beyond their function in plants, also as compounds with a wide range of biological and pharmacological activities, including cytostatic effect against various cancer cells. The nature and position of the substituents in the flavylium cation is essential for such biological properties, as well as the equilibrium between the multistate of the different chemical species that are generated by the flavylium cation, including quinoidal base, hemiketal, and cis- and trans-chalcones. In this work, eight new flavylium derivatives were synthesized, characterized for confirmation of the structure by FT-IR and 2D-NMR, and investigated in vitro as possible cytostatic compounds against HCT116 and HepG2 cancer cells. The most active two compounds were explored for their halochromic properties that can influence the biological activity and subjected to molecular encapsulation in ß-cyclodextrin derivatives in order to increase their solubility in water and bioavailability. The anticancer effect was influenced by the position (6-, 7-, or 8-) of the methoxy group in the ß-ring of the methoxy-4'-hydroxy-3'-methoxyflavylium cation, while the study of the halochromic properties revealed the important role played by the chalcone species of the pH-dependent multistate in both the uncomplexed and inclusion complex forms of these anthocyanidins.

Sustainable Stabilizer-Free Nanoparticle Formulations of Valsartan Using Eudragit® RLPO.

The bioavailability of the antihypertensive drug valsartan can be enhanced by various microencapsulation methods. In the present investigation, valsartan-loaded polymeric nanoparticles were manufactured from Eudragit® RLPO using an emulsion-solvent evaporation method. Polyvinyl alcohol (PVA) was found to be a suitable stabilizer for the nanoparticles, resulting in a monodisperse colloid system ranging in size between 148 nm and 162 nm. Additionally, a high encapsulation efficiency (96.4%) was observed. However, due to the quaternary ammonium groups of Eudragit® RLPO, the stabilization of the dispersion could be achieved in the absence of PVA as well. The nanoparticles were reduced in size (by 22%) and exhibited similar encapsulation efficiencies (96.4%). This more cost-effective and sustainable production method reduces the use of excipients and their expected emission into the environment. The drug release from valsartan-loaded nanoparticles was evaluated in a two-stage biorelevant dissolution set-up, leading to the rapid dissolution of valsartan in a simulated intestinal medium. In silico simulations using a model validated previously indicate a potential dose reduction of 60-70% compared to existing drug products. This further reduces the expected emission of the ecotoxic compound into the environment.

Poly(3-Hydroxybutyrate)-Based Nanoparticles for Sorafenib and Doxorubicin Anticancer Drug Delivery.

Dual drug-loaded nanotherapeutics can play an important role against the drug resistance and side effects of the single drugs. Doxorubicin and sorafenib were efficiently co-encapsulated by tailor-made poly([R,S]-3-hydroxybutyrate) (PHB) using an emulsion-solvent evaporation method. Subsequent poly(ethylene glycol) (PEG) conjugation onto nanoparticles was applied to make the nanocarriers stealth and to improve their drug release characteristics. Monodisperse PHB-sorafenib-doxorubicin nanoparticles had an average size of 199.3 nm, which was increased to 250.5 nm after PEGylation. The nanoparticle yield and encapsulation efficiencies of drugs decreased slightly in consequence of PEG conjugation. The drug release of the doxorubicin was beneficial, since it was liberated faster in a tumor-specific acidic environment than in blood plasma. The PEG attachment decelerated the release of both the doxorubicin and the sorafenib, however, the release of the latter drug remained still significantly faster with increased initial burst compared to doxorubicin. Nevertheless, the PEG-PHB copolymer showed more beneficial drug release kinetics in vitro in comparison with our recently developed PEGylated poly(lactic-co-glycolic acid) nanoparticles loaded with the same drugs.

Sustained in vitro interferon-beta release and in vivo toxicity of PLGA and PEG-PLGA nanoparticles.

Interferon-beta-1a (IFN-ß-1a) can diminish the symptoms of relapsing-remitting multiple sclerosis. Herein, we prepared sustained drug delivery IFN-ß-1a-loaded nanoparticles by a double emulsion solvent evaporation method. Bovine serum albumin (BSA) model drug was used to optimize the preparation of nanoparticles composed of four types of poly(lactic-co-glycolic acid) (PLGA) polymers and two pegylated PLGA (PEG-PLGA) polymers. Via optimization, selected PLGA and PEG-PLGA polymers were able to entrap IFN-ß-1a with high encapsulation efficiency (>95%) and low size (145 nm and 163 nm, respectively). In vitro release kinetics of BSA and IFN-ß showed similar tendency for PLGA and PEG-PLGA nanoparticles, respectively. Although the drug loaded nanoparticles did not show toxicity in hepatocyte cells, mild toxic effects such as pale kidney and pyelectasis were observed in the in vivo studies.

Preparation and in vitro characterization of valsartan-loaded ethyl cellulose and poly(methyl methacrylate) nanoparticles.

Valsartan is an antihypertensive drug used primarily orally, however, due to its hydrophobic nature it has got low bio-availability thus requiring higher dosage/frequency and causing more side effects. The aim of our work was to prepare valsartan-loaded nanoparticles by using ethyl cellulose and poly(methyl methacrylate) polymers which can be administered orally and to investigate the preparation conditions and their significance as potential drug carriers for valsartan delivery by in vitro release studies. Ethyl cellulose and poly(methyl methacrylate) polymers were used for the preparation of nanoparticles by single emulsion-solvent evaporation technique. The formation of drug-loaded nanoparticles was designed by experimental design for size and encapsulation efficiency, in addition the prepared nanosuspensions were nano spray dried in order to gain a powder form that is easy to handle and store. Both of the nano spray dried formulations had an amorphous structure in contrast to the pure drug according to differential scanning calorimetry and X-ray diffraction analysis, which can be advantageous in drug absorption. The originally processed ethyl cellulose-valsartan nanoparticles increased the solubility of the drug in the model intestinal medium, while poly(methyl methacrylate)-valsartan nanoparticles enabled substantially prolonged drug release. The release kinetics of both types of nanoparticles could be described by the Weibull model.

In vitro IFN-α release from IFN-α- and pegylated IFN-α-loaded poly(lactic-co-glycolic acid) and pegylated poly(lactic-co-glycolic acid) nanoparticles.

AIM: Interferon alpha (IFN-α) controlled release of nanoparticles was investigated under in vitro conditions. MATERIALS & METHODS: IFN-α and pegylated IFN-α (PEG-IFN-α) were encapsulated by poly(lactic-co-glycolic acid) (PLGA) and pegylated PLGA (PEG-PLGA) copolymers using double emulsion solvent evaporation method. RESULTS: The size of resulting four nanoparticles (IFN-α in poly(lactic-co-glycolic acids), IFN-α in poly(lactic-co-glycolic acid)-polyethylene glycol, PEG-IFN-α in poly(lactic-co-glycolic acids) and PEG-IFN-α in poly(lactic-co-glycolic acid)-polyethylene glycol) was below 130 nm diameter. IFN-α encapsulation efficiency of the nanoparticles was between 78 and 91%. CONCLUSION: The in vitro drug release studies conducted in phosphate-buffered saline and human plasma highlighted the role of incubation medium on the IFN release from the nanoparticles. The PEG-IFN-α in poly(lactic-co-glycolic acid)-polyethylene glycol was the most promising nanoparticle among the four formulations because of its remarkably constant release in both phosphate-buffered saline and plasma.

Polynuclear complexes of a dissociative excited state formed in the [Ru(bpy)2(CN)2]-HgCl2 system.

The complex cis-dicyanobis(2,2'-bipyridine)ruthenium(II) forms various bimetallic complexes with mercury(II)chloride, such as [(NC)Ru(bpy)2(CN)-HgCl2], [Cl2Hg-(NC)Ru(bpy)2(CN)-HgCl2-(NC)Ru(bpy)2(CN)-HgCl2] and [Cl2Hg-(NC)Ru(bpy)2(CN)-(HgCl2)] in CH3CN. These polynuclear complexes of the equilibrium system have been identified and characterized by their formation constants and absorption spectra. Excitation of bimetallic complexes produces the MLCT state localized on [Ru(bpy)2(CN)2] ligand, resulting in the cleavage of the bond formed between the nitrogen atom of the coordinated cyanide ligand and the Hg(II) central atom in ground state. Unlike many photoinduced metal ligand dissociations, the dissociated fragment remains in a luminescent excited state.