Polysaccharides in Ocular Drug Delivery

Polysaccharides, such as cellulose, hyaluronic acid, alginic acid, and chitosan, as well as polysaccharide derivatives, have been successfully used to augment drug delivery in the treatment of ocular pathologies. The properties of polysaccharides can be extensively modified to optimize ocular drug formulations and to obtain biocompatible and biodegradable drugs with improved bioavailability and tailored pharmacological effects. This review discusses the available polysaccharide choices for overcoming the difficulties associated with ocular drug delivery, and it explores the reasons for the dependence between the physicochemical properties of polysaccharide-based drug carriers and their efficiency in different formulations and applications. Polysaccharides will continue to be of great interest to researchers endeavoring to develop ophthalmic drugs with improved effectiveness and safety.Peer reviewe

Effect of Double Substitution in Cationic Chitosan Derivatives on DNA Transfection Efficiency

Recently, much effort has been expended on the development of non-viral gene delivery systems based on polyplexes of nucleic acids with various cationic polymers. Natural polysaccharide derivatives are promising carriers due to their low toxicity. In this work, chitosan was chemically modified by a reaction with 4-formyl-n,n,n-trimethylanilinium iodide and pyridoxal hydrochloride and subsequent reduction of the imine bond with NaBH4. This reaction yielded three novel derivatives, n-[4-(n',n',n'-trimethylammonium)benzyl]chitosan chloride (TMAB-CS), n-[(3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridine)methyl]chitosan chloride (Pyr-CS), and n-[4-(n',n',n''-trimethylammonium)benzyl]-n-[(3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridine)methyl]chitosan chloride (PyrTMAB-CS). Their structures and degrees of substitution were established by H-1 NMR spectroscopy as DS1 = 0.22 for TMAB-CS, DS2 = 0.28 for Pyr-CS, and DS1 = 0.21, DS2 = 0.22 for PyrTMAB-CS. Dynamic light scattering measurements revealed that the new polymers formed stable polyplexes with plasmid DNA encoding the green fluorescent protein (pEGFP-N3) and that the particles had the smallest size (110-165 nm) when the polymer:DNA mass ratio was higher than 5:1. Transfection experiments carried out in the HEK293 cell line using the polymer:DNA polyplexes demonstrated that Pyr-CS was a rather poor transfection agent at polymer:DNA mass ratios less than 10:1, but it was still more effective than the TMAB-CS and PyrTMAB-CS derivatives that contained a quaternary ammonium group. By contrast, TMAB-CS and PyrTMAB-CS were substantially more effective than Pyr-CS at higher polymer:DNA mass ratios and showed a maximum efficiency at 200:1 (50%-70% transfected cells). Overall, the results show the possibility of combining substituent effects in a single carrier, thereby increasing its efficacy.Peer reviewe

Влияние топологической структуры целлюлозы на процессы ацетилирования и нитрования

Эфиры целлюлозы активно используются при изготовлении новых полуфабрикатов, препаратов и материалов. Растительное сырье является основным источником для получения производных целлюлозы. Перспективным становится также производство целлюлозы путем микробиологического синтеза. Несмотря на одинаковые пути биосинтеза микрофибрилл, образцы целлюлозы растительного и бактериального происхождения отличаются по ряду структурных особенностей. Цель работы – оценка влияния топологической структуры целлюлозы растительного и бактериального происхождения на процессы ацетилирования и нитрования. В качестве образцов растительной целлюлозы использовали хлопковую и сульфатную целлюлозу. Бактериальную целлюлозу получали в лаборатории с применением смешанного сообщества микроорганизмов в статических условиях на синтетических глюкозных средах. Нитрование целлюлозы проводили смесью концентрированных H2SO4 и HNO3. Содержание азота в полученных образцах определяли ферросульфатным методом. ИК-спектры нитратов целлюлозы регистрировали на инфракрасном фурье-спектрометре Vertex-70 в диапазоне волновых чисел 4000…400 см–1. Ацетилирование целлюлозы осуществляли в среде сверхкритического диоксида углерода в системе сверхкритической флюидной экстракции SFE-5000, Thar Process. В ацетате целлюлозы титриметрически определяли содержание связанной уксусной кислоты, после чего рассчитывали степень замещения. Посредством электронной и атомно-силовой микроскопии визуализированы волокна растительной целлюлозы и фибриллы бактериальной целлюлозы. Выход нитрата из чистой хлопковой целлюлозы составил 160 %, т. е. степень замещения – 2,20. Нитрат целлюлозы, полученный из бактериальной целлюлозы в аналогичных условиях, имел степень замещения 1,96. Предложен новый метод прямого ацетилирования лиофильно высушенных препаратов бактериальной целлюлозы в среде сверхкритического диоксида углерода, что позволяет осуществлять процесс без кислотного катализатора и при пониженном расходе ацетилирующего агента. Ацетилирование растительной сульфатной целлюлозы показало степень замещения 2,40, для бактериальной целлюлозы – выход диацетилцеллюлозы с содержанием ацетильных групп 50 %, что соответствует степени замещения 2,10. Получение эфиров обусловлено как топохимическими особенностями микрофибрилл, так и кристалличностью материала. Для цитирования: Вашукова К.С., Терентьев К.Ю., Чухчин Д.Г., Ивахнов А.Д., Пошина Д.Н. Влияние топологической структуры целлюлозы на процессы ацетилирования и нитрования // Изв. вузов. Лесн. журн. 2023. № 6. С. 176–189. https://doi.org/10.37482/0536-1036-2023-6-176-18

Electrospun Polysaccharidic Textiles for Biomedical Applications

International audienceRecent developments in electrospinning technology have enabled the commercial-scale production of nonwoven fabrics from synthetic and natural polymers. Since the early 2000s, polysaccharides and their derivatives have been recognized as promising raw materials for electrospinning, and their electrospun textiles have attracted increasing attention for their diverse potential applications. In particular, their biomedical applications have been spotlighted thanks to their “green” aspects, e.g., abundance in nature, biocompatibility, and biodegradability. This review focuses on three main research topics in the biomedical applications of electrospun polysaccharidic textiles: (i) delivery of therapeutic molecules, (ii) tissue engineering, and (iii) wound healing, and discusses recent progress and prospects

Cellulose Cryogels as Promising Materials for Biomedical Applications

The availability, biocompatibility, non-toxicity, and ease of chemical modification make cellulose a promising natural polymer for the production of biomedical materials. Cryogelation is a relatively new and straightforward technique for producing porous light and super-macroporous cellulose materials. The production stages include dissolution of cellulose in an appropriate solvent, regeneration (coagulation) from the solution, removal of the excessive solvent, and then freezing. Subsequent freeze-drying preserves the micro- and nanostructures of the material formed during the regeneration and freezing steps. Various factors can affect the structure and properties of cellulose cryogels, including the cellulose origin, the dissolution parameters, the solvent type, and the temperature and rate of freezing, as well as the inclusion of different fillers. Adjustment of these parameters can change the morphology and properties of cellulose cryogels to impart the desired characteristics. This review discusses the structure of cellulose and its properties as a biomaterial, the strategies for cellulose dissolution, and the factors affecting the structure and properties of the formed cryogels. We focus on the advantages of the freeze-drying process, highlighting recent studies on the production and application of cellulose cryogels in biomedicine and the main cryogel quality characteristics. Finally, conclusions and prospects are presented regarding the application of cellulose cryogels in wound healing, in the regeneration of various tissues (e.g., damaged cartilage, bone tissue, and nerves), and in controlled-release drug delivery

Cytocompatibility of Bilayer Scaffolds Electrospun from Chitosan/Alginate-Chitin Nanowhiskers

In this work, a bilayer chitosan/sodium alginate scaffold was prepared via a needleless electrospinning technique. The layer of sodium alginate was electrospun over the layer of chitosan. The introduction of partially deacetylated chitin nanowhiskers (CNW) stabilized the electrospinning and increased the spinnability of the sodium alginate solution. A CNW concentration of 7.5% provided optimal solution viscosity and structurization due to electrostatic interactions and the formation of a polyelectrolyte complex. This allowed electrospinning of defectless alginate nanofibers with an average diameter of 200–300 nm. The overall porosity of the bilayer scaffold was slightly lower than that of a chitosan monolayer, while the average pore size of up to 2 μm was larger for the bilayer scaffold. This high porosity promoted mesenchymal stem cell proliferation. The cells formed spherical colonies on the chitosan nanofibers, but formed flatter colonies and monolayers on alginate nanofibers. The fabricated chitosan/sodium alginate bilayer material was deemed promising for tissue engineering applications

Chitin Cryogels Prepared by Regeneration from Phosphoric Acid Solutions

Cryogelation is a developing technique for the production of polysaccharide materials for biomedical applications. The formation of a macroporous structure during the freeze-drying of polysaccharide solutions creates biomaterials suitable for tissue engineering. Due to its availability, biocompatibility, biodegradability, and non-toxicity, chitin is a promising natural polysaccharide for the production of porous materials for tissue engineering; however, its use is limited due to the difficulty of dissolving it. This work describes the preparation of cryogels using phosphoric acid as the solvent. Compared to typical chitin solvents phosphoric acid can be easily removed from the product and recovered. The effects of chitin dissolution conditions on the structure and properties of cryogels were studied. Lightweight (ρ 0.025–0.059 g/cm3), highly porous (96–98%) chitin cryogels with various heterogeneous morphology were produced at a dissolution temperature of 20 ± 3 °C, a chitin concentration of 3–15%, and a dissolution time of 6–25 h. The crystallinity of the chitin and chitin cryogels was evaluated by 13C CP-MAS NMR spectroscopy and X-ray diffractometry. Using FTIR spectroscopy, no phosphoric acid esters were found in the chitin cryogels. The cryogels had compressive modulus E values from 118–345 kPa and specific surface areas of 0.3–0.7 m2/g. The results indicate that chitin cryogels can be promising biomaterials for tissue engineering

Biophysical Characterization and Cytocompatibility of Cellulose Cryogels Reinforced with Chitin Nanowhiskers

Polysaccharide-based cryogels are promising materials for producing scaffolds in tissue engineering. In this work, we obtained ultralight (0.046–0.162 g/cm3) and highly porous (88.2–96.7%) cryogels with a complex hierarchical morphology by dissolving cellulose in phosphoric acid, with subsequent regeneration and freeze-drying. The effect of the cellulose dissolution temperature on phosphoric acid and the effect of the freezing time of cellulose hydrogels on the structure and properties of the obtained cryogels were studied. It has been shown that prolonged freezing leads to the formation of denser and stronger cryogels with a network structure. The incorporation of chitin nanowhiskers led to a threefold increase in the strength of the cellulose cryogels. The X-ray diffraction method showed that the regenerated cellulose was mostly amorphous, with a crystallinity of 26.8–28.4% in the structure of cellulose II. Cellulose cryogels with chitin nanowhiskers demonstrated better biocompatibility with mesenchymal stem cells compared to the normal cellulose cryogels

Biocatalysis of Industrial Kraft Pulps: Similarities and Differences between Hardwood and Softwood Pulps in Hydrolysis by Enzyme Complex of Penicillium verruculosum

Kraft pulp enzymatic hydrolysis is a promising method of woody biomass bioconversion. The influence of composition and structure of kraft fibers on their hydrolysis efficiency was evaluated while using four substrates, unbleached hardwood pulp (UHP), unbleached softwood pulp (USP), bleached hardwood pulp (BHP), and bleached softwood pulp (BSP). Hydrolysis was carried out with Penicillium verruculosum enzyme complex at a dosage of 10 filter paper units (FPU)/g pulp. The changes in fiber morphology and structure were visualized while using optical and electron microscopy. Fiber cutting and swelling and quick xylan destruction were the main processes at the beginning of hydrolysis. The negative effect of lignin content was more pronounced for USP. Drying decreased the sugar yield of dissolved hydrolysis products for all kraft pulps. Fiber morphology, different xylan and mannan content, and hemicelluloses localization in kraft fibers deeply affected the hydrolyzability of bleached pulps. The introduction of additional xylobiase, mannanase, and cellobiohydrolase activities to enzyme mixture will further improve the hydrolysis of bleached pulps. A high efficiency of never-dried bleached pulp bioconversion was shown. At 10% substrate concentration, hydrolysates with more than 50 g/L sugar concentration were obtained. The bioconversion of never-dried BHP and BSP could be integrated into working kraft pulp mills