Doxorubicin aqueous systems at low concentrations: Interconnection between self-organization, fluorescent and physicochemical properties, and action on hydrobionts

Abstract

Doxorubicin (Dox) is a highly effective cytostatic antibiotic that exhibits activity against a wide range of malignant neoplasms and is often used as the basis of various anti-tumor compositions. However, the use of Dox in therapeutic doses is associated with high systemic toxicity, which makes it urgent to find ways to reduce therapeutic concentrations, which is necessary primarily to minimize the side effects on the patient’s body, as well as to reduce the harmful effects on aquatic ecosystems, commonly polluted by toxic pharmaceuticals. Studying the self-organization, physicochemical and spectral patterns, and their relation to bioeffects of Dox solutions in the range of low concentrations can reveal useful insights into the unknown effects of Dox as a cytostatic and potential pollutant of ecosystems. The self-organization in solutions and on substrates, physicochemical and spectral properties, and action of Dox solutions on hydrobionts were studied in the range of calculated concentrations from 1·10−20 to 1·10−4 M by methods of dynamic and electrophoretic light scattering (DLS and ELS), scanning electron microscopy (SEM), scanning probe microscopy (SPM), fluorescence spectroscopy, UV absorption spectroscopy, conductometry, tensiometry, pH-metry. Certified techniques for monitoring the toxicity of natural water and wastewater were used to establish the interconnection between these phenomena. It was shown that aqueous solutions of Dox are dispersed systems which rearrange their dispersed phase measuring hundreds of nm in size (nanoassociates) at dilution, followed by concerted changes in nanoassociates’ parameters (size and ζ-potential) and properties of systems, as well as their bioassay results. SPM and SEM results confirm and complement the DLS and ELS data indicating the existence of nanoassociates in dilute Dox solutions.

A Microfluidics-Assisted Double-Barreled Nanobioconjugate Synthesis Introducing Aprotinin as a New Moonlight Nanocarrier Protein: Tested toward Physiologically Relevant 3D-Spheroid Models

“…Correlating this phenomenon with the available literature, complex spectral methods (e.g., CD, DLS, UV−vis absorption, fluorescence, NMR, mass spectrometry, molecular dynamics) were used to establish that at concentrations in the range from 10 −3 to 10 −6 M, Dox molecules have a strong tendency to selfassociate through the stacking of aromatic chromophores and the formation of stacked dimers and/or higher order aggregates in aqueous solutions 34 Also, these results are in line with the study of Hakala et al 35 for HAS−drug nanoparticle formulations. Moreover, the optimized 100 μL/h flow rate provides sufficient throughput as compared to lower flow rates.…”

“…Correlating this phenomenon with the available literature, complex spectral methods (e.g., CD, DLS, UV–vis absorption, fluorescence, NMR, mass spectrometry, molecular dynamics) were used to establish that at concentrations in the range from 10 –3 to 10 –6 M, Dox molecules have a strong tendency to self-associate through the stacking of aromatic chromophores and the formation of stacked dimers and/or higher order aggregates in aqueous solutions…”

The Supramolecular Matrix Concept

“…Therefore, the idea that GrPs can be prepared only with the use of a solvent in which nanoassociates appear is not entirely correct. Traditionally, much attention is paid to nanoassociates as a factor that determines the activity of PD [55,90,[110][111][112]. Since PDs are dispersed-spatial structures that do not have a discrete carrier of activity, they do not have the fairly strict dependence of the effect on the dose, which is characteristic of conventional pharmacological preparations.…”

“…Therefore, the idea that GrPs can be prepared only with the use of a solvent in which nano-associates appear is not entirely correct. Traditionally, much attention is paid to nano-associates as a factor that determines the activity of PD [55,90,[110][111][112].…”

Changes in the Physico-Chemical and Biological Proper-Ties of Aqueous Solutions Under the Influence of Factors Modeling the Conditions of Space Flight

“…С использованием экотоксикологических тестов, допущенных для осуществления государственного экологического контроля токсичности питьевых, пресных природных и сточных вод, нами получена серия экспериментальных данных, свидетельствующих о взаимосвязи между параметрами наноассоциатов и спектральными характеристиками (УФ-, флуоресцентная спектроскопия) разбавленных систем БАВ, а также их воздействием на рост и развитие представителей водоемов -инфузорий Paramecium caudatum, рачков Ceriodaphnia affinis и одноклеточных зеленых водорослей Chlorella vulgaris [27-29, 32, 51-55]. Изучены самоорганизация и свойства разбавленных одно-и многокомпонентных водных систем практически важных биологически активных веществ и их композиций, таких как протеиногенная аминокислота L-триптофан, входящая в состав всех известных растительных и животных организмов [32]; янтарная кислота (ЯК), являющаяся при низкой концентрации биогенным регулятором метаболизма [28,51]; доксорубицин, высокоэффективный цитостатический антибиотик, проявляющий активность в моно-и комплексной терапии большого числа злокачественных новообразований [55]; многокомпонентный гербицидный препарат широкого спектра действия Раундап [54]; модельные композиции на основе Раундапа, доксорубицина и янтарной кислоты, потенциально пригодные для улучшения состояния водных экосистем, изменения токсичности антибиотика [29] Исследование влияния на гидробионты разбавленных растворов БАВ, таких как пестици-ды Раундап [54], метафос [52], фунгицид хлорацетофос [53], антибиотик доксорубицин [55], нестероидный противовоспалительный препарат диклофенак натрия [27], аминокислота L-триптофан [32], регулятор роста растений мелафен [33], янтарная и лимонная кислоты В последнее время в связи с расширением использования ионизирующего излучения ведутся активные разработки эффективных радиопротекторов. В целях выявления разбавленных систем БАВ, способных оказывать иммуномодулирующее и радиопротекторное действие, изучены самоорганизация, физико-химические и биологические свойства растворов отечественного препарата широкого спектра действия полиоксидония (ПО) [44,45].…”