Intravitreal hydrogels for sustained release of therapeutic proteins

This review highlights how hydrogel formulations can improve intravitreal protein delivery to the posterior segment of the eye in order to increase therapeutic outcome and patient compliance. Several therapeutic proteins have shown excellent clinical successes for the treatment of various intraocular diseases. However, drug delivery to the posterior segment of the eye faces significant challenges due to multiple physiological barriers preventing drugs from reaching the retina, among which intravitreal protein instability and rapid clearance from the site of injection. Hence, frequent injections are required to maintain therapeutic levels. Moreover, because the world population ages, the number of patients suffering from ocular diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) is increasing and causing increased health care costs. Therefore, there is a growing need for suitable delivery systems able to tackle the current limitations in retinal protein delivery, which also may reduce costs. Hydrogels have shown to be promising delivery systems capable of sustaining release of therapeutic proteins and thus extending their local presence. Here, an extensive overview of preclinically developed intravitreal hydrogels is provided with attention to the rational design of clinically useful intravitreal systems. The currently used polymers, crosslinking mechanisms, in vitro/in vivo models and advancements are discussed together with the limitations and future perspective of these biomaterials.Peer reviewe

Возможности праксеологии в банковской сфере

Статья посвящена исследованию сущности и возможностей использования основных постулатов и концептов праксеологии в банковской сфере. Изучаются особенности взаимодействия праксеологии как философско-логической сферы, с одной стороны, и банковского бизнеса как практической сферы деятельности – с другой. Проанализированы возможности внедрения в банковский сектор таких понятий, как «элементарные действия», «инициатор», а также использования критериев праксеологических оценок. Определены условия применимости «техники борьбы» для успешного функционирования коммерческого банка на рынке финансовых услуг.Статтю присвячено дослідженню сутності та можливостей використання основних постулатів і концептів праксеології в банківській сфері. Вивчаються особливості взаємодії праксеології як філософськологічної сфери, з одного боку, і банківського бізнесу як практичної сфери діяльності – з другого. Проаналізовано можливості впровадження в банківський сектор таких понять,як «елементарні дії», «ініціатор», а також використання критеріїв праксеологічних оцінок. Визначено умови застосування «техніки боротьби» для успішного функціонування комерційного банку на ринку фінансових послуг.The article is investigates the nature and possibilities of using the basic tenets and concepts of praxeology in the banking sector. We study the peculiarities of interaction of praxeology as a philosophical-logical sphere, on the one hand, and the banking business – both the practical scope of the other.The possibilities of implementation in the banking sector such concepts as «basic action», «initiator» as well as the use of criteria prakseologicheskih ratings. Indicated by the conditions of applicability «fighting techniques» for the successful operation of a commercial bank in the financial services market

Соціальна культура громадян - найкращий антикризовий засіб

An anthracene-functionalized thermosensitive block copolymer was synthesized, which formed micelles by heating its aqueous solution above the lower critical solution temperature (LCST). The micelles were subsequently crosslinked by UV illumination at 365 nm with a normal handheld UV lamp. The micelles showed a small size (30 nm) and high loading capacity (16.0 ± 0.1%) for paclitaxel and released paclitaxel for more than ten days

Этноконфликт как причина агрессии: проблема национальной безопасности Украины

Межэтнические и межнациональные противоречия являются сегодня одной из наиболее актуальных проблем многих стран мира, в том числе и Украины. Она относится к числу полиэтнических государств, где неизбежны межэтнические и межнациональные противоречия и конфликты. Анализу последних, их причин и возможных следствий и посвящена данная статья.Міжетнічні та міжнаціональні протиріччя сьогодні є однією з найбільш актуальних проблем багатьох країн світу, у тому числі і України. Вона належить до числа поліетнічних держав, де неминучі міжетнічні та міжнаціональні протиріччя та конфлікти, аналізу яких, їх причин і можливих наслідків присвячена дана стаття.Today interethnic and international contradictions are the most topical problems of many countries of the world including Ukraine. It belongs to those polyethnic states where interethnic and international contradictions and conflicts are unavoided. This article is devoted to analysis, causes and possible consequences of the last ones

Photopolymerized thermosensitive poly(HPMAlactate)-PEG-based hydrogels : effect of network design on mechanical properties, degradation, and release behavior

Photopolymerized thermosensitive A-B-A triblock copolymer hydrogels composed of poly(N-(2-hydroxypropyl)-methacrylamide lactate) A-blocks, partly derivatizal with methacrylate groups to different extents (10, 20, and 30%) and hydrophilic poly(ethylene glycol) B-blocks of different molecular weights (4, 10, and 20 kDa) were synthesized. The aim of the present study was to correlate the polymer architecture with the hydrogel properties, particularly rheological, swelling, degradation properties and release behavior. It was found that an increasing methacrylation extent and a decreasing PEG molecular weight resulted in increasing gel strength and cross-link density, which tailored the degradation profiles from 25 to more than 300 days. Polymers having small PEG blocks showed a remarkable phase separation into polymer- and water-rich domains, as demonstrated by confocal microscopy. Depending on the hydrophobic domain density, the loaded protein resides in the hydrophilic pores or is partitioned into hydrophilic and hydrophobic domains, and its release from these compartments is tailored by the extent of methacrylation and by PEG length, respectively. As the mechanical properties, degradation, and release profiles can be fully controlled by polymer design and concentration, these hydrogels are suitable for controlled protein release

Acrylamides with hydrolytically labile carbonate ester side chains as versatile building blocks for well-defined block copolymer micelles via RAFT polymerization

En route towards improved delivery systems for targeted chemotherapy, we propose a straightforward approach for the hydrophobic modification of the acrylamide N-(2-Hydroxyethyl) acrylamide (HEAm). An ethyl or benzyl group was introduced via a hydrolytically sensitive carbonate ester yielding HEAm-EC and HEAm-BC, respectively. Block copolymers of HEAm, respectively PEG and HEAm-EC or HEAm-BC were successfully synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, obtaining a library of well-defined block copolymers with different degrees of polymerization (DP). To further explore the versatility of our approach in terms of polymer synthesis, self-assembly, drug solubilization and in vitro cell interaction, polyethylene glycol (PEG) and polyHEAm as hydrophilic polymer blocks were compared. The block copolymers formed micellar nanoparticles (10-100 nm) in PBS and could efficiently solubilize hydrophobic dyes and anti-cancer drugs. Benzyl carbonate ester side chains increased micellar stability and drug loading capacity. Moreover, PEG as hydrophilic block showed in comparison to HEAm more promising results concerning both colloidal stability and drug loading capacity. Confocal microscopy showed that the micelles could efficiently deliver a hydrophobic dye inside the cells. Finally, we also demonstrated efficient formulation of the anti-cancer drug paclitaxel with an in vitro cancer cell killing performance comparable or even better than the two commercial PTX nano-formulations Abraxane and Genexol-PM at equal drug dose. In conclusion, modification of HEAm through carbonate linkages offers a versatile platform for the design of degradable polymers with potential for biomedical applications

Light-Triggered Cellular Delivery of Oligonucleotides

The major challenge in the therapeutic applicability of oligonucleotide-based drugs is the development of efficient and safe delivery systems. The carriers should be non-toxic and stable in vivo, but interact with the target cells and release the loaded oligonucleotides intracellularly. We approached this challenge by developing a light-triggered liposomal delivery system for oligonucleotides based on a non-cationic and thermosensitive liposome with indocyanine green (ICG) as photosensitizer. The liposomes had efficient release properties, as 90% of the encapsulated oligonucleotides were released after 1-minute light exposure. Cell studies using an enhanced green fluorescent protein (EGFP)-based splicing assay with HeLa cells showed light-activated transfection with up to 70%–80% efficacy. Moreover, free ICG and oligonucleotides in solution transfected cells upon light induction with similar efficacy as the liposomal system. The light-triggered delivery induced moderate cytotoxicity (25%–35% reduction in cell viability) 1–2 days after transfection, but the cell growth returned to control levels in 4 days. In conclusion, the ICG-based light-triggered delivery is a promising method for oligonucleotides, and it can be used as a platform for further optimization and development

Холотропное дыхание как метод реализации потенциала личности сотрудника

На сегодняшний день в организациях существует множество проблем, из-за которых возникают сложности как в управлении предприятием, так и в эффективной работе сотрудников. Для любого управляющего компанией важно, чтобы сотрудник был уверенным, умеющим нестандартно мыслить, инициативным, целеустремленным, но в большинстве случаев на предприятии такие сотрудники отсутствуют или их количество ограниченно. В любом сотруднике кроется творческая личность, которая не всегда может быть реализована на практике или же просто подавлена. Для того чтобы предприятие могло эффективно функционировать, важно, чтобы каждый сотрудник мог разобраться в своих проблемах и обрести внутреннюю гармонию, которая позволит ему настроиться на работу и выполнять ее эффективно. Методика холотропного дыхания может помочь личности реализовать свой скрытый потенциал. Цель работы: определить значимость методики холотропного дыхания в организации и выявить, какое влияние она оказывает как на сотрудников, так и на предприятие в целом. Методы исследования: анализ литера- туры по данной проблематике, аналитический метод. Результаты: выводы, полученные в данном исследовании, способствуют определению действенности методики холотропного дыхания и значимости ее применения в организации. Today there are many problems in organizations which lead to difficulties in the management of an enterpriseand in the effective work of the staff. For any company manager it is important that the employee wasconfident, able to think outside the box, initiative, committed, but in most cases such employees are absent ortheir number is limited. There is creative personality in any employee which can’t always be revealed or issimply suppressed. In order for a company to operate effectively, it is important that every employee couldunderstand their problems and find inner harmony, which will allow them to tune into work and perform itefficiently. The technique of holotropic breathwork can help the person to realize their hidden potential. Objective:to determine the significance of the technique of holotropic breathwork in the organization and itsimpact on the employees and the enterprise as a whole. Methods: review of the literature on this subject,data analysis. Results. The findings of this study help to identify the effective methods of holotropic breathworkand the importance of its application in the organization

Развитие инвестиционного кредитования в Украине

Free radical polymerization is often used to prepare protein and peptide-loaded hydrogels for the design of controlled release systems and molecular imprinting materials. Peroxodisulfates (ammonium peroxodisulfates (APS) or potassium peroxodisulfates (KPS)) with N,N,N,N-tetramethylethylenediamine (TEMED) are frequently used as initiator and catalyst. However, exposure to these free radical polymerization reagents may lead to modification of the protein and peptide. In this work, we show the modification of lysine residues by ammonium peroxodisulfate (APS)/TEMED of the immunostimulant thymopentin (TP5). Parallel studies on a decapeptide and a library of 15 dipeptides were performed to reveal the mechanism of modification. LC-MS of APS/TEMED-exposed TP5 revealed a major reaction product with an increased mass (+12 Da) with respect to TP5. LC-MS2 and LC-MS3 were performed to obtain structural information on the modified peptide and localize the actual modification site. Interpretation of the obtained data demonstrates the formation of a methylene bridge between the lysine and arginine residue in the presence of TEMED, while replacing TEMED with a sodium bisulfite catalyst did not show this modification. Studies with the other peptides showed that the TEMED radical can induce methyleneation on peptides when lysine is next to arginine, proline, cysteine, aspargine, glutamine, histidine, tyrosine, tryptophan, and aspartic acid residues. Stability of peptides and protein needs to be considered when using APS/TEMED in in situ polymerization systems. The use of an alternative catalyst such as sodium bisulfite may preserve the chemical integrity of peptides during in situ polymerization