Структура комплекса включения дисульфирама с гидроксипропил-β-циклодекстрином

Disulfiram is an inhibitor of superoxide dismutase, reduced lipid peroxidation, and can be an effective pharmaceutical substance for the treatment of cataracts. Unfortunately, the use of disulfiram in ophthalmology is limited due to its practically insoluble in water. Hydroxypropyl-β-cyclodextrin is an effective solubilizing agent and has long been used in the pharmaceutical industry. Due to its structure hydroxypropyl-β-cyclodextrin forms inclusion complexes with pharmaceutical substance which soluble in water is limited. In this paper it was investigated a new method of obtaining inclusion complex of hydroxypropyl-β-cyclodextrin with disulfiram. Inclusion complex prepared and isolated in powder form, the formation of inclusion complex and its physicochemical properties was confirmed by X-ray powder diffraction and UVspectrophotometry.На основании проведенных исследований предложен метод получения комплекса включения дисульфирама с гидроксипропил-β-циклодекстрином. Разработанная методология позволила получить комплекс включения в порошкообразном виде, изучить его физико-химические свойства и подтвердить образование комплекса включения методами порошковой рентгеновской дифракции и УФ-спектрофотометрии

ИССЛЕДОВАНИЕ ФОТОСЕНСИБИЛИЗАТОРА ДЛЯ АНТИБАКТЕРИАЛЬНОЙ ФОТОДИНАМИЧЕСКОЙ ТЕРАПИИ НА ОСНОВЕ ЦИКЛОДЕКСТРИНОВОЙ КОМПОЗИЦИИ МЕТИЛОВОГО ЭФИРА 133-N-(N-МЕТИЛНИКОТИНИЛ) БАКТЕРИОПУРПУРИНИМИДА

Cationic bacteriochlorins are promising as antibacterial photosensitizers (PS) for antibacterial photodynamic therapy. Current work is devoted to the study of properties of new nanostructured cationic photosensitizer based on cyclodextrin dispersion of bacteriochlorine derivative – 133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester, for optimization of dispersion composition and selection of time interval between administration of the PS and photodynamic ttherapy of infected septic wounds. Specifics of absorption and fluorescence of PS in dependence of its concentration and proportions of components in dispersion was assessed. Pharmacokinetics and biodistribution of PS were studies in vivo in organs and tissues of intact mice and septic wounds infected with P. аeruginosa or S. aureus. The preliminary studies have shown high efficiency of antimicrobial photodynamic therapy of septic wounds with cyclodextrin dispersion of 133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester. Results of study of absorption and spectral and fluorescence properties of its drug formulation depending on its composition allowed to recommend the use of weight ratio 133-N-(N-methylnicotinyl)bacteriopurpurinimide methyl ester : cyclodextrin about 1:200 and addition of 0,1% Tween 80 to reduce aggregation. The study showed that 133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester was rapidly cleared from mouse blood circulation: more than 70% – for 2 h, 95% – for 1 day, more than 99% – for 6 days. About 98% was cleared from skin and muscles for 6 days. The long-term (up to 24 h) persistence of PS were observed in liver and kidneys, however more than 99% was cleared for 6 days. Thus, it may be supposed that elimination of PS form mice body is through kidneys and liver. After 24 h partial PS aggregation in tissues, particularly in skin and muscles, was observed. Thus, it may be supposed that the reduce of fluorescence intensity after 24 hand later was associated not only with its elimination from body but with its aggregation. Spectral and fluorescence studies showed that 133-N-(Nmethylnicotinyl)-bacteriopurpurinimide methyl ester selectively accumulated in septic wounds, fluorescence contrast was in the range of 3–4. The highest values of concentration and selectivity of its accumulation were achieved at 1.5–3 h after intravenous injection. The irradiation 2 h after injection provided high efficacy of the therapy of septic wounds.Катионные бактериохлорины перспективны как антимикробные фотосенсибилизаторы для антибактериальной фотодинамической терапии. Настоящая работа посвящена изучению свойств нового наноструктурированного катионного фотосенсибилизатора на основе циклодекстриновой дисперсии производного бактериохлорина – метилового эфира 133-N-(N-метилникотинил)бактериопурпуринимида (КБХ), с целью оптимизации состава дисперсии и выбора интервала времени от введения фотосенсибилизатора до проведения фотодинамической терапии инфицированных гнойных ран. Оценены особенности поглощения и флуоресценции фотосенсибилизатора в зависимости от его концентрации и соотношения между компонентами дисперсии. Изучена фармакокинетика и биораспределение фотосенсибилизатора в органах и тканях интактных мышей и гнойных ранах, инфицированных P. аeruginosa или S. aureus. Предварительные исследования показали высокую эффективность антимикробной фотодинамической терапии инфицированных гнойных ран с циклодекстрированной дисперсией КБХ. Проведенные исследования поглощения и спектрально-флуоресцентных свойств его лекарственной формы в зависимости от ее состава позволили рекомендовать использование массового отношения КБХ : циклодекстрин около 1:200 и введение для уменьшения агрегации 0,1% Твин-80. Установлено, что КБХ быстро выводится из кровотока мыши: более 70% – за 2 ч, 95% – за 1 сут , более 99% – за 6 сут. Из кожи и мышц около 98% выводится за 6 сут. Фотосенсибилизатор накапливается и удерживается до 24 ч в печени и почках. Это позволяет предположить, что элиминирование фотосенсибилизатора из организма мышей происходит через почки и печень. Обнаружено, что в тканях, в частности, в коже и мышцах, через 24 ч наблюдается частичная агрегация фотосенсибилизатора. Это позволяет предположить, что уменьшение интенсивности его флуоресценции через 24 и более часа связано не только с его элиминацией из организма, но и с агрегацией. Спектрально-флуоресцентное исследования показали, что КБХ селективно накапливается в инфицированных ранах, флуоресцентная контрастность лежит в пределах 3–4. Наиболее высокие значения концентрации и селективности его накопления в инфицированных ранах были достигнуты через 1,5–3 ч после внутривенного введения. Облучение через 2 ч после введения обеспечило высокую эффективность терапии инфицированных гнойных ран

STANDARDIZATION OF INCLUSION COMPLEX OF DISULFIRAM WITH HYDROXYPROPYL-β-CYCLODEXTRIN FOR USE AS PHARMACEUTICAL SUBSTANCES

The State Pharmacopoeia XIII sets out the main principles of quality of pharmaceutical substances listed parametrs that should be included in the regulatory documents, given the characteristics of these indicators and recommendations for their regulation. Input quality control performance and valuation limits must comply with the appointment of the pharmaceutical substance. This paper presents the key indicators that can be used to standardize the inclusion complex of disulfiram with hydroxypropyl-β-cyclodextrin for later use as a pharmaceutical substance

CYCLODEXTRINS AND THEIR APPLICATION IN PHARMACEUTICAL INDUSTRY (REVIEW)

In the review describes the main properties of cyclodextrins and their potential use in the formulations in various dosage forms as excipients, by which it becomes possible to modify the solubility of drugs, increase the bioavailability and stability of the drug

Structure of inclusion complex of disulfiram with hydroxypropyl-β-cyclodextrin

Disulfiram is an inhibitor of superoxide dismutase, reduced lipid peroxidation, and can be an effective pharmaceutical substance for the treatment of cataracts. Unfortunately, the use of disulfiram in ophthalmology is limited due to its practically insoluble in water. Hydroxypropyl-β-cyclodextrin is an effective solubilizing agent and has long been used in the pharmaceutical industry. Due to its structure hydroxypropyl-β-cyclodextrin forms inclusion complexes with pharmaceutical substance which soluble in water is limited. In this paper it was investigated a new method of obtaining inclusion complex of hydroxypropyl-β-cyclodextrin with disulfiram. Inclusion complex prepared and isolated in powder form, the formation of inclusion complex and its physicochemical properties was confirmed by X-ray powder diffraction and UVspectrophotometry

Hydrophilic nature and sorption-diffusion properties of nanocomposite hybrid polysulfone films

Hybrid nanocomposite films containing silica (≥11.4 wt.%) or titania (≥18.8 wt.%) in the polymer matrix were prepared by the sol-gel method using the hydrolytic polycondensation of tetraethoxysilane and tetrabutoxysilane in a THF solution of aromatic polymer, polysulfone (PSF). The influence of the oxide nature and the film composition on the structure, the interaction of the polymer with oxides, hydrophilicity, and sorption-diffusion properties of the hybrid films were studied by FTIR spectroscopy, atomic force microscopy, dynamic light scattering, and a complex of other physicochemical methods. The absence of chemical or intermolecular hydrogen bonds between the polymer and oxide particles in the PSF films was shown. The average size of the oxides (SiO 2, ∼20 nm; TiO2, ∼90 nm) in the films and roughness of their surface (∼0.2-0.8 nm) were determined. The introduction of oxides into the polymer matrix increases the hydrophilic properties and the ability of the PSF films to swell in water; the diffusion coefficients of water and permeability of water vapor in the PSF films also increase. Titania also induces a more considerable change in the structure of the polymer matrix and more strongly affects the sorption-diffusion properties of the hybrid films in aqueous solutions of THF. All prepared nanocomposite films PSF/SiO2 and PSF/TiO2 are capable of extracting an organic component from aqueous solutions and can be used as sorbents and membrane films for the removal of organic substances from the aqueous medium. © 2012 Springer Science+Business Media New York

Gold and Arsenic in Pyrite and Marcasite: Hydrothermal Experiment and Implications to Natural Ore-Stage Sulfides

Hydrothermal synthesis experiments were performed in order to quantify the states of Au and As in pyrite and marcasite. The experiments were performed at 350 °C/500 bar and 490 °C/1000 bar (pyrite–pyrrhotite buffer, C(NaCl) = 15 and 35 wt.%). The synthesis products were studied by EPMA, LA-ICP-MS, and EBSD. The EPMA was applied for simultaneous determinations of Au, As, Fe, and S, with a Au detection limit of 45–48 ppm (3σ). The analyses were performed along profiles across zonal grains. The concentrations of As and Au up to 5 wt.% and 8000 ppm, respectively, were determined in pyrite and up to 6 wt.% and 1300 ppm in marcasite. In pyrite, the Au concentration decreases with fluid salinity and temperature increases. Strong positive Au–As correlation and strong negative Au–Fe and As–S correlation were identified in pyrite. Comparison of the correlations with theoretical lines implies Au–As clustering. The cluster stoichiometry is inferred to be [AuAs10]. Most probably, As in pyrite presents in the form of clusters and in the As→S solid solution. Incorporation of Au in As-rich pyrite can be controlled by the reductive deposition mechanism. In marcasite, the concentrations of Au are not correlated with the As content. The [AuAs10] clusters enrich the {210}, {113}, and {111} pyrite faces, where the former exhibits the highest affinity to Au and As. The affinity of {110} and {100} forms to Au and As is lower. Implication of the experimental results to data for natural auriferous pyrite shows that the increase of Au content at C(As) > 0.5–1 wt.% is caused by the incorporation of the Au-As clusters, but not because of the formation of Au→Fe solid solution. Therefore, the concentration of “invisible” gold in pyrite is dictated solely by the hydrothermal fluid chemistry and subsequent ore transformations

STUDY OF PHOTOSENSITIZER FOR ANTIBACTERIAL PHOTODYNAMIC THERAPY BASED ON CYCLODEXTRIN FORMULATION OF 133-N-(N-METHYLNICOTINYL)BACTERIOPURPURINIMIDE METHYL ESTER

Cationic bacteriochlorins are promising as antibacterial photosensitizers (PS) for antibacterial photodynamic therapy. Current work is devoted to the study of properties of new nanostructured cationic photosensitizer based on cyclodextrin dispersion of bacteriochlorine derivative – 133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester, for optimization of dispersion composition and selection of time interval between administration of the PS and photodynamic ttherapy of infected septic wounds. Specifics of absorption and fluorescence of PS in dependence of its concentration and proportions of components in dispersion was assessed. Pharmacokinetics and biodistribution of PS were studies in vivo in organs and tissues of intact mice and septic wounds infected with P. аeruginosa or S. aureus. The preliminary studies have shown high efficiency of antimicrobial photodynamic therapy of septic wounds with cyclodextrin dispersion of 133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester. Results of study of absorption and spectral and fluorescence properties of its drug formulation depending on its composition allowed to recommend the use of weight ratio 133-N-(N-methylnicotinyl)bacteriopurpurinimide methyl ester : cyclodextrin about 1:200 and addition of 0,1% Tween 80 to reduce aggregation. The study showed that 133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester was rapidly cleared from mouse blood circulation: more than 70% – for 2 h, 95% – for 1 day, more than 99% – for 6 days. About 98% was cleared from skin and muscles for 6 days. The long-term (up to 24 h) persistence of PS were observed in liver and kidneys, however more than 99% was cleared for 6 days. Thus, it may be supposed that elimination of PS form mice body is through kidneys and liver. After 24 h partial PS aggregation in tissues, particularly in skin and muscles, was observed. Thus, it may be supposed that the reduce of fluorescence intensity after 24 hand later was associated not only with its elimination from body but with its aggregation. Spectral and fluorescence studies showed that 133-N-(Nmethylnicotinyl)-bacteriopurpurinimide methyl ester selectively accumulated in septic wounds, fluorescence contrast was in the range of 3–4. The highest values of concentration and selectivity of its accumulation were achieved at 1.5–3 h after intravenous injection. The irradiation 2 h after injection provided high efficacy of the therapy of septic wounds