Исследования в области создания эффективных лекарственных препаратов нового поколения включением классических субстанций в наноконтейнеры

Biopharmaceutical technologies using phospholipids for the development of a new generation of pharmaceutical formulations are considered. Industrial methods for isolating phosphatidylcholine from egg yolk and cardiolipin from the heart muscle were implemented at the Biolek company (Kharkov). The industrial production of a number of phospholipid fractions has been mastered too. The latest data concerning the application of nanocontainers for loading classic drugs during the design of modern effective drug formulations are reported. These formulations are used to improve the results of treatment, to provide the targeted drug delivery into pathological foci, to prolong the action time, and to increase the drug solubility. Among the aforementioned containers, special emphasis should be given to liposomes, nanosomal polymeric formulations based on polybutylcyanoacrylates or on polylactides, and spherical amorphous nanoparticles formed from birch bark triterpenoids. The modern state of researches performing by scientific team headed by academician V.I. Shvets is also presented.Рассмотрены биофармацевтические технологии на основе фосфолипидов и их применение в разработке медицинских препаратов нового поколения с использованием наноконтейнеров разного типа. Представлено современное состояние исследований, проводимых научным коллективом под руководством академика В.И. Швеца, в этой области

Производные мио-инозита нелипидной природы - получение и применение для биомедицинских целей

The structures, properties and possibilities for biomedical applications of myo-inositol non-lipid derivatives are reviewed.Рассмотрены строение, свойства и потенциал биомедицинского применения нелипидных производных мио-инозита

РАЦИОНАЛЬНЫЙ СПОСОБ ПОЛУЧЕНИЯ ПСЕВДОПЕПТИДНЫХ ФРАГМЕНТОВ – КЛЮЧЕВЫХ ИНТЕРМЕДИАТОВ СИНТЕЗА ПОЛИАМИДНЫХ МИМЕТИКОВ НУКЛЕИНОВЫХ КИСЛОТ (ПАНКМ)

The convenient synthesis of the key structure fragments of polyamide nucleic acid mimic (PANAM) monomers according to route using Mitsunobu’s reaction and subsequent thiolysis of protective o-nitrobenzenesulphonyl group is presented. The purification of target secondary amines was occurred after the thiolysis stage by an extraction at various pH, without isolation of fully protected pseudopeptide intermediate derivatives. Thus, it were obtained BocGlyΨAlaOAll, BocAlaΨGlyOMe, BocGluΨGlyOAll, BocGlyΨGlyOMe, CbzAlaΨGlyOMe, CbzGlu(Ot Bu)ΨGlyOMe. It was shown that yields of target compounds are comparable both by the employing of purification stage of intermediates and without it. The key condition of successful applying of presented method is the absence of initial “acid component” in the reaction mixture undertaken to thiolysis.П редставлена универсальная схема синтеза ключевых фрагментов полиамидных миметиков нуклеиновых кислот с использованием реакции Мицунобу и последующим тиолизом защитной о-нитробензолсульфонильной группы. Очистку целевых вторичных аминов осуществляли экстракцией при различных pH, без выделения промежуточного полностью защищенного псевдо-пептидного фрагмента. Показано, что выходы целевых соединений сопоставимы как при использовании стадии очистки промежуточных соединений, так и без нее

Синтез двух тиминсодержащих мономеров ПНК на основе L-аланина и глицина

Effective preparative synthesis of two thymine containing monomers of polyamide DNA-mimics based on L-alanine and glycine is presented. The results of investigation are more effective steps for allyl ester protective group incorporation and coupling of thymin-1-yl acetic acid with pseudopeptide intermediate.Представлен эффективный препаративный синтез двух тиминсодержащих мономеров полиамидных ДНК-миметиков на основе производных L-аланина и глицина. В результате исследования оптимизированы стадии введения аллильной защиты и конденсации тимин-1-илуксусной кислоты с псевдопептидным интермедиатом

НАУЧНАЯ ШКОЛА АКАДЕМИКА В.И. ШВЕЦА: БИОНАНОФАРМАЦЕВТИЧЕСКИЕ ТЕХНОЛОГИИ ИННОВАЦИОННЫХ ЛЕКАРСТВЕННЫХ ПРЕПАРАТОВ НАПРАВЛЕННОГО ДЕЙСТВИЯ И ПОДГОТОВКА КАДРОВ

The results of many years of scientific research in the field of physico-chemical biology and its most important direction - lipidology, conducted by the leading scientific school under the leadership of Academician RAS Vitaly I. Shvets, are reported. On the creation of synthetic, biotechnological methods for obtaining lipids, with the possibility of their practical use by designing on this basis effective diagnostic and medicinal products and application in practical medicine. The further development and use of methods of bionanotechnology for the development of modern medicines for directed action on the basis of increasing the effectiveness of classical drugs by their incorporation into nanocontainers is described. It is reported on the development of technologies for obtaining nanoscale forms of drugs, the study of their pharmacological properties and use in medical practice. Information is provided on the preparation of liposomal antitumor, hepatoprotective, anti-tuberculosis, cardiac preparations based on the proposed echnologies, the study of properties and the use for therapeutic purposes. The technologies for obtaining and conducting biological studies of nanoforms based on copolymers of lactic and glycolic acids of antineoplastic, anti-inflammatory, antibacterial and a number of other drugs have been developed: It has been shown that the use of nanosized drugs can lead to a significant increase in the pharmacological effect due to various factors. It was noted that during the construction of the drug for the treatment of Parkinson's disease, the contents of liposomes loaded with dopamine pass through the blood-brain barrier almost 100 times better than individual dopamine molecules. Finding a substance in nanoparticles reduces its toxicity primarily due to the effect of "passive targeting". The prolonged action of medicinal substances enclosed in nanoparticles is discussed, due to their gradual release. It is noted that the targeted delivery of nanoparticles makes it possible to increase the effectiveness of the drugs by an order of magnitude. It is reported on the drug-delivery technology in the field of oncology and the use of the method of selective delivery of cytostatics to tumor tissues using the receptor-mediated endocytosis. Biological and pharmacological studies based on nanopoporous silicon on the creation of liposomal drugs for the treatment of cancer, cardiological pathologies, tuberculosis are carried out. Data on the work of the scientific and educational center for training specialists in the field of biotechnology and pharmacy are given.Сообщается о результатах многолетней научно-исследовательской работы в области физико-химической биологии и важнейшего ее направления - липидологии, проводимой ведущей научной школой под руководством академика РАН В.И. Швеца по созданию синтетических, биотехнологических методов получения липидов, с возможностью практического их использования путем конструирования на этой основе эффективных диагностических и лекарственных препаратов и применения в медицине. Описано дальнейшее развитие и использование методов бионанотехнологии для создания современных лекарственных средств направленного действия на базе повышения эффективности классических препаратов включением их в наноконтейнеры. Сообщается о разработке технологий получения наноразменых форм лекарственных препаратов, исследовании их фармакологических свойств и использовании в медицинской практике. Приводятся сведения о получении на основе предложенных технологий, изучении свойств и применении в лечебных целях липосомальных противоопухолевых, гепатопротекторных, противотуберкулезных, кардиологических препаратов. Созданы технологии получения и проведены биологические исследования наноформ на основе сополимеров молочной и гликолевой кислот противоопухолевых, противоинсультных, антибактериальных и ряда других препаратов. Показано, что использование наноразмерных лекарств может приводить к значительному увеличению фармакологического эффекта за счет разных факторов. Так, отмечается, что в процессе конструирования препарата для лечения болезни Паркинсона содержимое липосом, нагруженных дофамином, проходит через гематоэнцефалический барьер практически в 100 раз лучше, чем отдельные молекулы дофамина. Нахождение субстанции в наночастицах снижает ее токсичность прежде всего вследствие эффекта «пассивного нацеливания». Обсуждается пролонгированное действие лекарственных субстанций, заключенных в наночастицы, за счет их постепенного высвобождения. Отмечено, что адресная доставка наночастиц позволяет на порядок увеличить эффективность действия лекарств. Сообщается о технологии направленного транспорта лекарственных препаратов (drug-delivery) в области онкологии и об использовании метода избирательной доставки цитостатиков в опухолевые ткани с использованием рецептор-опосредованного эндоцитоза. Проводятся биологические и фармакологические исследования на основе нанопопористого кремния по созданию липосомальных лекарственных препаратов для лечения рака, кардиологических патологий, туберкулеза. Приведены данные о работе научно-образовательного центра по подготовке специалистов в области биотехнологии и фармации

The research applicable to elaboration of new generation of effective medicinal drugs using encapsulation of classic substances into nanocontainers

Biopharmaceutical technologies using phospholipids for the development of a new generation of pharmaceutical formulations are considered. Industrial methods for isolating phosphatidylcholine from egg yolk and cardiolipin from the heart muscle were implemented at the Biolek company (Kharkov). The industrial production of a number of phospholipid fractions has been mastered too. The latest data concerning the application of nanocontainers for loading classic drugs during the design of modern effective drug formulations are reported. These formulations are used to improve the results of treatment, to provide the targeted drug delivery into pathological foci, to prolong the action time, and to increase the drug solubility. Among the aforementioned containers, special emphasis should be given to liposomes, nanosomal polymeric formulations based on polybutylcyanoacrylates or on polylactides, and spherical amorphous nanoparticles formed from birch bark triterpenoids. The modern state of researches performing by scientific team headed by academician V.I. Shvets is also presented

Nonlipid myo-inositol derivatives: preparation and biomedical applications

The structures, properties and possibilities for biomedical applications of myo-inositol non-lipid derivatives are reviewed

Efficient approach for producing pseudopeptide fragments – the key intermediates of the synthesis of polyamide nucleic acid mimics (PANAM)

The convenient synthesis of the key structure fragments of polyamide nucleic acid mimic (PANAM) monomers according to route using Mitsunobu’s reaction and subsequent thiolysis of protective o-nitrobenzenesulphonyl group is presented. The purification of target secondary amines was occurred after the thiolysis stage by an extraction at various pH, without isolation of fully protected pseudopeptide intermediate derivatives. Thus, it were obtained BocGlyΨAlaOAll, BocAlaΨGlyOMe, BocGluΨGlyOAll, BocGlyΨGlyOMe, CbzAlaΨGlyOMe, CbzGlu(Ot Bu)ΨGlyOMe. It was shown that yields of target compounds are comparable both by the employing of purification stage of intermediates and without it. The key condition of successful applying of presented method is the absence of initial “acid component” in the reaction mixture undertaken to thiolysis

Synthesis of two PNA thymine monomers based on L-alanine and glycine

Effective preparative synthesis of two thymine containing monomers of polyamide DNA-mimics based on L-alanine and glycine is presented. The results of investigation are more effective steps for allyl ester protective group incorporation and coupling of thymin-1-yl acetic acid with pseudopeptide intermediate

SCIENTIFIC SCHOOL OF ACADEMICIAN VITALY I. SHVETS: BIONANOPHARMACEUTICAL TECHNOLOGIES OF INNOVATIVE DIRECTED-ACTION MEDICINAL PREPARATIONS AND MANPOWER TRAINING

The results of many years of scientific research in the field of physico-chemical biology and its most important direction - lipidology, conducted by the leading scientific school under the leadership of Academician RAS Vitaly I. Shvets, are reported. On the creation of synthetic, biotechnological methods for obtaining lipids, with the possibility of their practical use by designing on this basis effective diagnostic and medicinal products and application in practical medicine. The further development and use of methods of bionanotechnology for the development of modern medicines for directed action on the basis of increasing the effectiveness of classical drugs by their incorporation into nanocontainers is described. It is reported on the development of technologies for obtaining nanoscale forms of drugs, the study of their pharmacological properties and use in medical practice. Information is provided on the preparation of liposomal antitumor, hepatoprotective, anti-tuberculosis, cardiac preparations based on the proposed echnologies, the study of properties and the use for therapeutic purposes. The technologies for obtaining and conducting biological studies of nanoforms based on copolymers of lactic and glycolic acids of antineoplastic, anti-inflammatory, antibacterial and a number of other drugs have been developed: It has been shown that the use of nanosized drugs can lead to a significant increase in the pharmacological effect due to various factors. It was noted that during the construction of the drug for the treatment of Parkinson's disease, the contents of liposomes loaded with dopamine pass through the blood-brain barrier almost 100 times better than individual dopamine molecules. Finding a substance in nanoparticles reduces its toxicity primarily due to the effect of "passive targeting". The prolonged action of medicinal substances enclosed in nanoparticles is discussed, due to their gradual release. It is noted that the targeted delivery of nanoparticles makes it possible to increase the effectiveness of the drugs by an order of magnitude. It is reported on the drug-delivery technology in the field of oncology and the use of the method of selective delivery of cytostatics to tumor tissues using the receptor-mediated endocytosis. Biological and pharmacological studies based on nanopoporous silicon on the creation of liposomal drugs for the treatment of cancer, cardiological pathologies, tuberculosis are carried out. Data on the work of the scientific and educational center for training specialists in the field of biotechnology and pharmacy are given