Biopolymer-based multilayer capsules and beads made via templating : advantages, hurdles and perspectives

One of the undeniable trends in modern bioengineering and nanotechnology is the use of various biomolecules, primarily of a polymeric nature, for the design and formulation of novel functional materials for controlled and targeted drug delivery, bioimaging and theranostics, tissue engineering, and other bioapplications. Biocompatibility, biodegradability, the possibility of replicating natural cellular microenvironments, and the minimal toxicity typical of biogenic polymers are features that have secured a growing interest in them as the building blocks for biomaterials of the fourth generation. Many recent studies showed the promise of the hard-templating approach for the fabrication of nano- and microparticles utilizing biopolymers. This review covers these studies, bringing together up-to-date knowledge on biopolymer-based multilayer capsules and beads, critically assessing the progress made in this field of research, and outlining the current challenges and perspectives of these architectures. According to the classification of the templates, the review sequentially considers biopolymer structures templated on non-porous particles, porous particles, and crystal drugs. Opportunities for the functionalization of biopolymer-based capsules to tailor them toward specific bioapplications is highlighted in a separate section

Naturally derived nano- and micro-drug delivery vehicles: halloysite, vaterite and nanocellulose

Recent advances in drug delivery and controlled release had a great impact on bioscience, medicine and tissue engineering. Consequently, a variety of advanced drug delivery vehicles either have already reached the market or are approaching the phase of commercial production. Progressive growth of the drug delivery market has led to the necessity to earnestly concern about economically viable, up-scalable and sustainable technologies for a large-scale production of drug delivery carriers. We have identified three attractive natural sources of drug carriers: aluminosilicate clays, minerals of calcium carbonate, and cellulose. Three classes of drug delivery carriers derived from these natural materials are halloysite nanotubes, vaterite crystals and nanocellulose. These carriers can be produced using “green” technologies from some of the most abundant sources on the Earth and have extremely high potential to meet all criteria applied for the manufacture of modern delivery carriers. We provide an up-to-date snapshot of these drug delivery vehicles towards their use for bioapplications, in particular for drug delivery and tissue engineering. The following research topics are addressed: (i) the availability, sources and methodologies used for production of these drug delivery vehicles, (ii) the drug loading and release mechanisms of these delivery vehicles, (iii) in vitro, in vivo, and clinical studies on these vehicles, and (iv) employment of these vehicles for tissue engineering. Finally, the prospects for vehicles’ further development and industrialisation are critically assessed, highlighting most attractive future research directions such as the design of third generation active biomaterials

Porous alginate scaffolds assembled using vaterite CaCO3 crystals

Formulation of multifunctional biopolymer-based scaffolds is one of the major focuses in modern tissue engineering and regenerative medicine. Besides proper mechanical/chemical properties, an ideal scaffold should: (i) possess a well-tuned porous internal structure for cell seeding/growth and (ii) host bioactive molecules to be protected against biodegradation and presented to cells when required. Alginate hydrogels were extensively developed to serve as scaffolds, and recent advances in the hydrogel formulation demonstrate their applicability as “ideal” soft scaffolds. This review focuses on advanced porous alginate scaffolds (PAS) fabricated using hard templating on vaterite CaCO3 crystals. These novel tailor-made soft structures can be prepared at physiologically relevant conditions offering a high level of control over their internal structure and high performance for loading/release of bioactive macromolecules. The novel approach to assemble PAS is compared with traditional methods used for fabrication of porous alginate hydrogels. Finally, future perspectives and applications of PAS for advanced cell culture, tissue engineering, and drug testing are discussed

Effect of a Type of Loading on Stresses at a Planar Boundary of a Nanomaterial

Abstract A two-dimensional model of an elastic body at nanoscale is considered as a half-plane under the action of a periodic load at the boundary. An additional surface stress, and constitutive equations of the Gurtin-Murdoch surface linear elasticity are assumed. Using Goursat-Kolosov complex potentials and Muskhelisvili technique, the solution of the boundary value problem in the case of an arbitrary load is reduced to a hypersingular integral equation in an unknown surface stress. For the case of a periodic load, the solution of this equation is found in the form of Fourier series. The influence of the surface stress on the stresses at the boundary of the half-plane under the tangential and normal periodic loading is analyzed. In particular, it is found out the size effect which becomes apparent in the dependence of the stresses on a length of the load period of the order 10 nm. Moreover, the tangential stresses appear under the action of the normal loads

ГЕОДИНАМИЧЕСКИЕ ВОЛНЫ И ГРАВИТАЦИЯ

 Gravity phenomena related to the Earth movements in the Solar System and through the Galaxy are reviewed. Such movements are manifested by geological processes on the Earth and correlate with geophysical fields of the Earth. It is concluded that geodynamic processes and the gravity phenomena (including those of cosmic nature) are related.  The state of the geomedium composed of blocks is determined by stresses with force moment and by slow rotational waves that are considered as a new type of movements [Vikulin, 2008, 2010]. It is shown that the geomedium has typical rheid properties [Carey, 1954], specifically an ability to flow while being in the solid state [Leonov, 2008]. Within the framework of the rotational model with a symmetric stress tensor, which is developed by the authors [Vikulin, Ivanchin, 1998; Vikulin et al., 2012a, 2013], such movement of the geomedium may explain the energy-saturated state of the geomedium and a possibility of its movements in the form of vortex geological structures [Lee, 1928]. The article discusses the gravity wave detection method based on the concept of interactions between gravity waves and crustal blocks [Braginsky et al., 1985]. It is concluded that gravity waves can be recorded by the proposed technique that detects slow rotational waves. It is shown that geo-gravitational movements can be described by both the concept of potential with account of gravitational energy of bodies [Kondratyev, 2003] and the nonlinear physical acoustics [Gurbatov et al., 2008]. Based on the combined description of geophysical and gravitational wave movements, the authors suggest a hypothesis about the nature of spin, i.e. own moment as a demonstration of the space-time ‘vortex’ properties.   Проводится обзор гравитационных явлений, связанных с движениями Земли в Солнечной системе и Галактике. Эти движения и их вариации отражаются в геологических процессах, происходящих в Земле, и коррелируют с ее геофизическими полями. Формулируется вывод о существовании взаимосвязи между геодинамическими процессами и гравитационными (космической природы в том числе) явлениями. Состояние геосреды, являющейся блоковой по своему строению, определяется напряжениями с моментом силы и новым типом движений – медленными ротационными волнами [Vikulin, 2008a, 2008b, 2010]. Показано, что для гео­среды характерны реидные [Carey, 1953] свойства – способность течь в твердом состоянии [Leonov, 2008]. Такое движение геосреды позволяет в рамках развиваемой авторами ротационной модели с симметричным тензором напряжений [Vikulin, Ivanchin, 1998; Vikulin et al., 2012a, 2013] объяснить ее энергонасыщенное состояние и возможность движения в виде вихревых геологических структур [Lee, 1928]. Обсуждается метод регистрации гравитационных волн, в основе которого заложена идея их взаимодействия с блоками земной коры [Braginsky et al., 1985]. Формулируется вывод о том, что в рамках такой методики с использо­ванием в качестве детектора медленных ротационных волн оказывается возможным зарегистрировать гравитационные волны. Описание геогравитационных движений возможно в рамках как теории потенциала с учетом гравитационной энергии тел [Kondratiev, 2003], так и нелинейной физической акустики [Gurbatov et al., 2008]. Обобщение гео­физических и гравитационных волновых движений позволило авторам предложить гипотезу о природе спина – собственного момента как проявления «вихревых» свойств пространства–времени. 

МИГРАЦИЯ СЕЙСМИЧЕСКОЙ И ВУЛКАНИЧЕСКОЙ АКТИВНОСТИ КАК ПРОЯВЛЕНИЕ ВОЛНОВОГО ГЕОДИНАМИЧЕСКОГО ПРОЦЕССА

Publications about the earthquake foci migration have been reviewed. An important result of such studies is establishment of wave nature of seismic activity migration that is manifested by two types of rotational waves; such waves are responsible for interaction between earthquakes foci and propagate with different velocities. Waves determining long-range interaction of earthquake foci are classified as Type 1; their limiting velocities range from 1 to 10 cm/s. Waves determining short-range interaction of foreshocks and aftershocks of individual earthquakes are classified as Type 2; their velocities range from 1 to 10 km/s. According to the classification described in [Bykov, 2005], these two types of migration waves correspond to slow and fast tectonic waves. The most complete data on earthquakes (for a period over 4.1 million of years) and volcanic eruptions (for 12 thousand years) of the planet are consolidated in a unified systematic format and analyzed by methods developed by the authors. For the Pacific margin, Alpine-Himalayan belt and the Mid-Atlantic Ridge, which are the three most active zones of the Earth, new patterns of spatial and temporal distribution of seismic and volcanic activity are revealed; they correspond to Type 1 of rotational waves. The wave nature of the migration of seismic and volcanic activity is confirmed. A new approach to solving problems of geodynamics is proposed with application of the data on migration of seismic and volcanic activity, which are consolidated in this study, in combination with data on velocities of movement of tectonic plate boundaries. This approach is based on the concept of integration of seismic, volcanic and tectonic processes that develop in the block geomedium and interact with each other through rotating waves with a symmetric stress tensor. The data obtained in this study give grounds to suggest that a geodynamic value, that is mechanically analogous to an impulse, remains constant in such interactions. It is thus shown that the process of wave migration of geodynamic activity should be described by models with strongly nonlinear equations of motion.Проведен обзор работ по миграции очагов землетрясений. Важным результатом явилось установление волновой природы миграции сейсмической активности, которая осуществляется  двумя типами ротационных волн, ответственными за взаимодействие очагов землетрясений и распространяющимися с разными скоростями. Первому типу с предельными скоростями 1–10 см/с соответствуют волны, определяющие дальнодействующее взаимодействие очагов землетрясений, второму – с предельными скоростями 1–10 км/с – соответствуют волны, определяющие близкодействующее взаимодействие форшоков и афтершоков в пределах отдельно взятых очагов землетрясений. Согласно классификации [Bykov, 2005], такие типы волн миграции соответствуют медленным и быстрым тектоническим волнам. В едином формате представлены наиболее полные данные о землетрясениях за 4.1 тыс. лет и извержениях вулканов за 12 тыс. лет. Собранные данные систематизированы и проанализированы с помощью разработанных авторами методик. Для трех наиболее активных поясов Земли – Пацифики, Альпийско-Гималайского и Срединно-Атлантического – установлены новые, отвечающие первому типу ротационных волн, закономерности пространственно-временного распределения сейсмической и вулканической активности. Подтверждена волновая природа их миграции. Полученные в работе данные в совокупности с данными о скоростях движения границ тектонических плит предлагается использовать в качестве нового подхода к решению задач геодинамики. В основе такого подхода заложена идея единства сейсмического, вулканического и тектонического процессов, протекающих в блоковой геосреде и взаимодействующих между собой посредством ротационных волн с симметричным тензором напряжений. Полученные авторами данные позволяют предположить, что при таком взаимодействии сохраняется геодинамическая величина, механическим аналогом которой является импульс. Показано, что процесс волновой миграции геодинамической активности должен описываться в рамках моделей с сильно нелинейными уравнениями движения

Vaterite-nanosilver hybrids with antibacterial properties and pH-triggered release

Silver nanoparticles (AgNPs) have been used for over a century in various applications due to their distinctive properties. Nonetheless, the poor stability of AgNPs and adverse effects on living organisms have driven the search for materials able to protect and better control their release. Vaterite CaCO3 crystals have been studied in the last two decades as carriers for different drugs due to their biocompatibility, easy synthesis and pH-sensitive properties. Herein, AgNPs were loaded into vaterite to protect, store, and control their release, resulting in CaCO3/AgNPs hybrids. To tune the release of the AgNPs, the recrystallization of the hybrids into thermodynamically more stable calcite was studied and modulated with carboxymethyledextran (DexCM) and poly(4-styrenesulfonic acid) sodium salt (PSS), with the last one being able to stabilise the hybrids and prevent a premature release of the AgNPs at low contents (2%, w/w). The release of AgNPs from the hybrids was studied at pH 5 to 9, showing a pH-dependent release suppression for PSS-stabilised hybrids. Various mathematical models were applied to clarify the release mechanism, confirming the role of PSS in stabilising and targeting the release of AgNPs. The antibacterial studies demonstrated that the hybrids protect the AgNPs without affecting their activity, with the released nanoparticles being effective against Escherichia coli, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Overall, this work sheds light on the release mechanisms of AgNPs from the inorganic hybrids helping to foresee the release profiles of other compounds from vaterite

Hybrid Mucin‐Vaterite Microspheres for Delivery of Proteolytic Enzyme Chymotrypsin

Abstract While the enteral delivery of proteolytic enzymes is widely established for combating many diseases as an alternative to antibiotic treatment, their local delivery only emerges as administration route enabling sustained release in a controlled manner on site. The latest requires the development of drug delivery systems suitable for encapsulation and preservation of enzymatic proteolytic activity. This study proposes hybrid microspheres made of mucin and biodegradable porous crystals of calcium carbonate (CC) as the carriers for chymotrypsin (CTR) delivery. CTR is impregnated into CC and hybrid CC/mucin (CCM) microspheres by means of sorption without any chemical modification. The loading of the CC with mucin enhances CTR retention on hybrid microspheres (adsorption capacity of ≈8.7 mg g−1 vs 4.7 mg g−1), recharging crystal surface due to the presence of mucin and diminishing the average pore diameter of the crystals from 25 to 8 nm. Mucin also retards recrystallization of vaterite into nonporous calcite improving stability of CCM microspheres upon storage. Proteolytic activity of CTR is preserved in both CC and CCM microspheres, being pH dependent. Temperature‐induced inactivation of CTR significantly diminishes by CTR encapsulation into CC and CCM microspheres. Altogether, these findings indicate promises of hybrid mucin‐vaterite microspheres for mucosal application of proteases

Immobilization of Antioxidant Enzyme Catalase on Porous Hybrid Microparticles of Vaterite with Mucin

Catalase is one of the crucial antioxidant enzymes with diverse applications in textile, food industries, wastewater treatment, cosmetics, and pharmaceutics, which, however, is highly sensitive to environmental challenges. Resisting the loss of activity and prolongation of formulation storage can be achieved via the catalase entrapment into insoluble carriers. Affordable and degradable vaterite is proposed as amicable material for catalase immobilization. To improve the carrier properties of the vaterite, it was co‐precipitated with mucin from the pig's stomach producing ca 5 μm hybrid mucin/vaterite microparticles. Catalase is impregnated into the crystals by means of adsorption without chemical modifications. The presence of mucin matrix partially hinders catalase penetration into the crystals and reduces the adsorption capacity (for 0.1 mg mL−1 catalase, ca 2.3 vs ca 1.5 mg g−1 for pristine and hybrid microparticles, respectively) but significantly promotes the protection of antioxidant activity upon storage and under the action of temperature, organic solvent (acetonitrile), and proteolytic enzyme (trypsin). Hybrid microcrystals are pH‐sensitive and better retain the enzyme at pH 3–5 due to catalase‐mucin complexation. Immobilized catalase can be used for 5–6 consecutive cycles until it loses catalytic activity. Altogether, these findings indicate promises of hybrid mucin/vaterite microparticles for immobilization of antioxidant enzymes

Эффективность применения модификаций препарата Суперстим в малых дозах на этапе адаптации микрорастений жимолости (Lonicera L.) подсекции синей (Caeruleae Rehd.) к нестерильным условиям с учетом последействия на этапе доращивания

Relevance. In recent years, interest in the edible honeysuckle culture has increased in Russia, the wide distribution of which is hampered by the lack of quality planting material. The technology of clonal micropropagation allows for a short time to obtain a large amount of honeysuckle planting material, more than a thousand regenerated plants per year from one meristematic apex introduced into an in vitro culture. It is hundreds of times more than in traditional methods of vegetative propagation. Adaptation to non-sterile conditions is the final and most crucial stage of clonal micropropagation, the loss of which can be from 50 to 90%. It should be noted that there is practically no research on how the further development of adapted honeysuckle plants takes place during subsequent growing.Methods. Researching of growth regulators of the new generation Superstim 1 and Superstim 2 effect in low and ultra-low doses on the survival rates and development of honeysuckle plants at the stages of adaptation subsequent growing.Results. Superstim 1 is more effective at physiological concentrations – 1 x 10-7 and in the field of ultra-low doses – 1 x 10-14, 1 x 10-15%. At the stage of subsequent growing, a positive after-effect of physiological concentrations – 1x10-3 and 1x10-7 was observed, and an ultra-low dose – 1x10-17%. The growth regulator Superstim 2 at the stages of adaptation and subsequent growing is effectively used only in one concentration – 1x10-16%. The additional foliar treatments at the stage of subsequent growing are not necessary. Актуальность. В последние годы в России увеличивается интерес к культуре жимолости съедобной, широкое распространение которой сдерживается из-за дефицита качественного посадочного материала. Технология клонального микроразмножения позволяет за короткий срок получить большое количество посадочного материала жимолости, более тысячи растений-регенерантов в год из одного введенного в культуру in vitro меристематического апекса, что в сотни раз больше, чем при использовании традиционных методов вегетативного размножения. Адаптация к нестерильным условиям является заключительным и наиболее ответственным этапом клонального микроразмножения, потери на котором могут составлять от 50 до 90% мериклонов. Следует отметить, что практически нет исследований о том, каким образом происходит дальнейшее развитие адаптированных растений жимолости при доращивании.Методика. Проведено изучение влияния препаратов нового поколения Суперстим 1 и Суперстим 2 в малых и сверхмалых дозах на показатели приживаемости и развития растений жимолости на этапах адаптации и доращивания.Результаты. Выявлено, что препарат Суперстим 1 более эффективен в физиологической концентрации – 1x10-7% и в области сверхмалых доз – 1x10-14, 1x10-15%. На этапе доращивания выявлено положительное последействие физиологических концентраций – 1x10-3, 1x10-7%, и сверхмалой дозы – 1x10-17%. Препарат Суперстим 2 на этапах адаптации и доращивания эффективно применять только в одной концентрации – 1x10-16%. В дополнительных некорневых обработках на этапе доращивания нет необходимости.