Local Drug Delivery in Bladder Cancer: Advances of Nano/Micro/Macro-Scale Drug Delivery Systems.

Treatment of bladder cancer remains a critical unmet need and requires advanced approaches, particularly the development of local drug delivery systems. The physiology of the urinary bladder causes the main difficulties in the local treatment of bladder cancer: regular voiding prevents the maintenance of optimal concentration of the instilled drugs, while poor permeability of the urothelium limits the penetration of the drugs into the bladder wall. Therefore, great research efforts have been spent to overcome these hurdles, thereby improving the efficacy of available therapies. The explosive development of nanotechnology, polymer science, and related fields has contributed to the emergence of a number of nanostructured vehicles (nano- and micro-scale) applicable for intravesical drug delivery. Moreover, the engineering approach has facilitated the design of several macro-sized depot systems (centimeter scale) capable of remaining in the bladder for weeks and months. In this article, the main rationales and strategies for improved intravesical delivery are reviewed. Here, we focused on analysis of colloidal nano- and micro-sized drug carriers and indwelling macro-scale devices, which were evaluated for applicability in local therapy for bladder cancer in vivo.

The Effect of Bean Seed Treatment with Entomopathogenic Fungus Metarhizium robertsii on Soil Microarthropods (Acari, Collembola).

The treatment of agricultural crops with entomopathogenic fungi may disturb the structure of soil microarthropod communities, which can have an adverse impact on soil fertility and, ultimately, on the yield. The effect of the treatment of broad bean (Vicia faba L.) seeds, with the entomopathogenic fungus Metarhizium robertsii, on the abundance and community structure of soil microarthropods in the rhizosphere was assessed in different phases of plant vegetation in a two-year experiment. Under the conditions of the gradually decreased abundance of M. robertsii both in the soil cenoses and in the plants during summer, no adverse effect was revealed of the bean seed treatment, with the entomopathogenic fungus, on the abundance of soil microarthropods (Acari: Mesostigmata, Prostigmata, Oribatida and Astigmata; Collembola) and the structure of their communities. Similar results were obtained in the analysis, taking into account the positive colonization of plants. Some changes in the microarthropod community structure were explained primarily by the spatial heterogeneity of the field, the hydrothermal regime, and the features of the microarthropod life cycles. The results indicate the possibility of using dressing seeds with conidial suspension for plant inoculation with entomopathogenic fungus (at least M. robertsii) as a potentially safe plant protection method for non-target soil microarthropods.

Description of new genus Baikalozercon (Acari: Mesostigmata: Zerconidae) with two new species from South Siberia Mountains (Russia).

This paper describes a new genus and two new species of mites in the family Zerconidae collected from litter and soil in the South Siberia Mountains. Baikalozercon gen. nov. is described to accommodate two new species B. dracunculus sp. nov. and B. irbis sp. nov. on the basis of adults specimens and immature stages. The new genus is characterised by unique characters such as very large size of idiosoma (9001000 m length); long peritremes in adults reaching to coxae I; sexual dimorphism of male gnathosomal structures; modified fixed digit of chelicerae with extended apical edge and large apical outgrowth; a pair of massive subcapitular denticles located between h3 and pc setae in B. dracunculus sp. nov.; and modified setae on legs II.

Distribution, habitats, and redescription of the rare mite species emIphidonopsis/em emsculptus/em Gwiazdowicz, 2004 (Mesostigmata: Ascidae).

Iphidonopsis sculptus Gwiazdowicz, 2004, is currently known only from the type locality in eastern Poland and a record in southwestern Finland (Huhta, 2016). Here, we record this species from twelve localities elsewhere (Europe, Siberia, Far East of Russia, Canada) indicating its broadly Holarctic geographical range. Another genus member, Iphidonopsis magnanalis (Ma Yin, 1999), is known only from China. About half of Iphidonopsis sculptus records are associated with litter of coniferous or mixed forests, but the others, including samples with juveniles (deutonymphs), were found in bracket fungi or under tree bark. The finding of two adult females on a bark beetle, Dryocoetes affaber (Mannerheim) (Coleoptera: Curculionidae: Scolytinae), suggests a phoretic association, though members of the closely related genus Zerconopsis Hull, 1918 as well as of all of the subfamily Arctoseiinae are known only from phoretic dispersal by nematoceran dipterans. The morphology of adults and an immature instar (deutonymph) of I. sculptus is redescribed and newly described, respectively, and illustrated in detail. A subdivision of the subfamily Arctoseiinae Evans, 1963 into three tribes is proposed-Arctoseiini Evans, 1963 (including Arctoseius Thor, 1930 and Iphidozercon Berlese, 1903), Zerconopsini tribe n. (Zerconopsis Hull, 1918; Xenoseius Lindquist Evans, 1965; and Iphidonopsis Gwiazdowicz, 2004), and Maxiniini tribe n. (Maxinia Lindquist Makarova, 2012).

Four new species of Halozercon (Acari: Mesostigmata: Zerconidae) from South Siberia Mountains (Russia) with a key to all known species.

Four new species of zerconid mites of the genus Halozercon are described and illustrated based on material collected from litter and soil in Altai and Tuva mountains, South Siberia, Russia-H. alataus sp. n., H. gryphus sp. n., H. kumir sp. n. and H. aesopi sp. n. Morphological characters for the new Halozercon species are given. A key for all known species of Halozercon is attached.

A new species of the genus Proctogastrolaelaps McGraw amp; Farrier (Acari: Melicharidae) from the Far East of Russia, and contributions to knowledge of this genus.

We describe a new mite species from the Far East of RussiaProctogastrolaelaps subsolanus Joharchi Marchenko sp. nov. (Acari: Melicharidae). The new species was collected from soil-litter on the shores of the Tunaycha Lake and Sea of Okhotsk in Sakhalin Island. The important morphological characteristics of the genus Proctogastrolaelaps are revised.

Three new species of Halozercon (Acari: Mesostigmata: Zerconidae) from Altai Mountains in South Siberia (Russia).

Three new species of zerconid mites of the genus Halozercon are described and illustrated: H. tigerek sp. n., H. kazachok sp. n. and H. capitaneus sp. n., on the basis of material collected from litter and soil in the Altai Mountains in South Siberia, Russia. Morphological characters of adults, nymphs and larva for new Halozercon species are given.

Composite materials based on Ag nanoparticles in situ synthesized on the vaterite porous matrices.

We have designed sensors based on Ag nanoparticles synthesized in situ on the vaterite beads. In this article we demonstrate an approach to produce size controllable spherical and elliptical vaterite particles and discuss time-dependent in situ Ag nanoparticles synthesis and its potential effect on surface-enhanced Raman scattering. The time dependent silver reduction synthesis in inorganic porous particles allows to regulate the number and size of Ag nanoparticles. It is shown that the irregular surface and high porosity of vaterite particles and large amount (surface filling factor) of the Ag nanoparticles are the critical parameters to increase the SERS signal to 104 times. Such inorganic composites have a huge potential in medical applications; soon they provide an opportunity to study intracellular processes in vivo. The detailed characterization of the microstructure of these composites was studied by scanning and transmission electron microscopy, including 3D visualization and energy dispersive x-ray microanalysis.

[The analysis of association between ENPP1 K121Q polymorphism and risk factors of type 2 diabetes mellitus in ukrainian population].

OBJECTIVE: Introduction: More than 100 genes have been described associations between single nucleotide polymorphisms and type 2 diabetes mellitus (T2DM). Among these candidate genes, Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1), is located on the long arm of chromosome 6 (6q23.2) and encodes for a protein which is one of the factors determining the insulin sensitivity. An allelic polymorphism in exon 4 of ENPP1 (rs1044498) has been designated K121Q and widely investigated in T2DM in different populations. The aim: To analyze the association between ENPP1 K121Q polymorphism with the risk factors of type 2 diabetes mellitus in the Ukrainian population. PATIENTS AND METHODS: Materials and methods: Venous blood of 317 patients with type 2 diabetes mellitus and 302 controls was used for analysis. ENPP1 K121Q genotyping was performed using PCR-RFLP method. RESULTS: Results: Our results revealed that ratio of K/K homozygotes, K/Q heterozygotes and Q/Q homozygotes between case and control groups was significantly different (59.3%, 34.1%, 6.6% vs 67.9%, 28.5%, 3.6%, P = 0.05). Method of binary logistic regression shown that a reliable relationship was established in the general group for KQ/QQ vs K/K genetic model (P = 0.027). It was shown that in carriers of the minor Q-allele, the risk of T2DM is 1.4x higher than in homozygotes in the main K-allele (95% CI = 1.043-2.016). After adjusting for age, sex, smoking habit, BMI, obesity and the presence of hypertension, the reliability of these results persisted (P = 0.026). CONCLUSION: Conclusions: ENPP1 K121Q polymorphism is associated with T2DM in Ukrainian population. In carriers of the minor Q-allele the risk of T2DM is 1.4x higher than in homozygotes in the main K-allele. The risk increases in patients with BMI ≥ 25 kg/m2.

A novel formulation of zolpidem for direct nose-to-brain delivery: synthesis, encapsulation and intranasal administration to mice.

OBJECTIVES: Anxiolytic drug zolpidem was incorporated into the microcontainers based on mesoporous calcium carbonate particles modified by diethylaminoethyl-dextran/hyaluronic acid shell. The release of zolpidem in saline solution and in polymer film modelling nasal mucosa was investigated. The anxiolytic effect of zolpidem upon intranasal administration of microcontainers and free medicine was determined by in vivo experiments on mice. METHODS: The structures of all compounds during zolpidem synthesis were established using nuclear magnetic resonance spectroscopy. The loading efficacy and release kinetics of zolpidem were analysed by spectrophotometry. Surface morphology of formulation was investigated by scanning electron microscopy. To determine the effect of zolpidem-loaded containers administration by the intranasal route in vivo experiments was carried out applying the open field test. KEY FINDINGS: Nasal administration of zolpidem in the form of the microcontainers based on mesoporous calcium carbonate particles modified by diethylaminoethyl-dextran/hyaluronic acid shell has a pronounced anxiolytic effect on the behaviour of the animals in the open field test. CONCLUSIONS: The polyelectrolyte shell deposited together with zolpidem enhances the loading efficacy of the microcontainers. In vivo experiments on mice demonstrate increase in anxiolytic effect of zolpidem in microcontainers compared with upon intranasal administration of free medicine.

[The association between enpp1 rs997509 polymorphism and type 2 diabetes mellitus development in ukrainian population].

OBJECTIVE: Introduction: Genome-Wide Association Studies have identified a large number of polymorphic loci associated with type 2 diabetes mellitus (T2DM). Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) gene is one of the candidate genes which have primary importance in T2DM development. Several studies revealed the association between ENPP1 polymorphisms, including rs997509, and T2DM, obesity, insulin resistance and metabolic syndrome in different populations. The aim: To test the association between ENPP1 rs997509 polymorphism and T2DM development in patients with different risk factors in the Ukrainian population. PATIENTS AND METHODS: Materials and methods: Venous blood of 317 unrelated T2DM patients and 302 healthy volunteers was used for analysis. ENPP1 rs997509 genotyping was performed using PCR-RFLP (polymerase chain reaction with following restriction fragment length polymorphism analysis) method. RESULTS: Results: Our results revealed that ratio of C/C homozygotes, C/T heterozygotes and T/T homozygotes between case and control groups was significantly different (89.0 % , 11.0%, 0 % vs 94.4 %, 5.6 %, 0 %, P = 0.015). It was shown that risk of T2DM development in T allele carriers is significantly higher compared to C/C homozygotes (OR = 2.086; P= 0.027). Herewith the risk increased in heterozygotes with BMI ≥ 25 kg/m2 (OR = 2.223, P=0.031) and obesity (OR = 3.230; P = 0.023). CONCLUSION: Conclusions: ENPP1 rs997509 polymorphism is associated with T2DM development in Ukrainian population.

A new species of Halozercon (Acari: Zerconidae) from South Siberia (Russia) with additional information on Halozercon karacholana Wisniewski et al., 1992.

Halozercon barguzin sp. nov. is described and illustrated based on female, male, deutonymph and protonymph specimens collected from soil and litter in the Khamar-Daban Range of South Baikal Region (South Siberia, Russia). Additional morphological information and illustrations of all developmental stages of of Halozercon karacholana Wisniewski et al., 1992 are provided, with new data on its geographical distribution.

Mesoporous particle-based microcontainers for intranasal delivery of imidazopyridine drugs.

The aim of this study was to develop mesoporous containers for entrapment of imidazopyridines, such as sedative-hypnotic medicine zolpidem, anxiolytic agent alpidem and their derivatives. For this purpose, calcium carbonate (size 1.2 µm (PDI: 0.6), zeta potential: -10 mV), manganese carbonate (2.5 µm (PDI: 0.5), zeta potential: -12 mV) and titanium dioxide particles (3.7 µm (PDI: 0.4), zeta potential: -15 mV) were used. The compounds were encapsulated applying two techniques: adsorption on the preformed particles and co-precipitation during the synthesis of the particles. The polymer shell of the containers was formed by electrostatic adsorption of polyelectrolytes on the surface of the particles. The best encapsulation efficacy was shown for zolpidem incorporated into calcium carbonate (5.4%) and manganese carbonate (4.6%) by adsorption. Release of the compounds from the containers based on the proposed particles were characterised by the short time burst effect (<10 min) followed by desorption prolongation by formation of polymer shell. X-ray microtomography results demonstrate the prolonged retention of the containers with the mucoadhesive shell in the nasal cavity.

A new species of Neparholaspis (Acari: Parholaspididae) from Russia, with additional information on Neparholaspis evansi Krantz, 1960.

Neparholaspis dubatolovi sp. nov. is described and illustrated from adult females and males collected from litter and moss in montane forest in north-eastern Sikhote-Alin Ridge in the Far East of Russia. Additional morphological information and illustrations of Neparholaspis evansi Krantz, 1960 are provided, based on examination of a paratype. A key to the world species of Neparholaspis is provided.

A new species of Pachyseius Berlese (Acari: Pachylaelapidae) from South Siberia (Russia), with a key to the species known from Asia.

Pachyseius anisimovi sp. nov. is described based on specimens from soil and litter in the Altai Mountains and the West and East Sayan Mountains in South Siberia, Russia. A key to ten Pachyseius species known from Asia is provided. 

A new species of Gamasiphis Berlese (Acari: Ologamasidae) from North Asia, with a key to the Eurasian species.

Gamasiphis angaridis sp. n. is described from females and males collected from litter and soil in the North Asian part of Russia-Siberia and the Far East. This is the first species of the large genus Gamasiphis to be described from the northern Palaearctic Region. A key for the separation of females of the 11 recognisable species of Gamasiphis described in Eurasia is provided.

A new species of Gamasiphis Berlese (Acari: Ologamasidae) from Russia (Sakhalin and Kuril Islands) with a key to the Asian species .

Gamasiphis ochotensis sp. n. is described based on the morphology of females and males collected from litter and soil in the Sakhalin and Kuril Islands of Far East Russia. A key for the separation of females of 10 recognisable species of Gamasiphis distributed in Asia is provided.

Controlled enzyme-catalyzed degradation of polymeric capsules templated on CaCO3: influence of the number of LbL layers, conditions of degradation, and disassembly of multicompartments.

Enzyme-catalyzed degradation of CaCO3-templated capsules is presented. We investigate a) biodegradable, b) mixed biodegradable/synthetic, and c) multicompartment polyelectrolyte multilayer capsules with different numbers of polymer layers. Using confocal laser scanning microscopy we observed the kinetics of the non-specific protease Pronase-induced degradation of capsules is slowed down on the order of hours by either increasing the number of layers in the wall of biodegradable capsules, or by inserting synthetic polyelectrolyte multilayers into the shell comprised of biodegradable polymers. The degradation rate increases with the concentration of Pronase. Controlled detachment of subcompartments of multicompartment capsules, with potential for intracellular delivery or in-vivo applications, is also shown.