CC BY
6
УДК 541.64
DOI: 10.33184/bulletin-bsu-2022.1.6
THE INFLUENCE OF MEDICAL SUBSTANCE NATURE ON CONFORMATION AND SUPRAMOLECULAR STATES OF CARBOXYMETHYLCELLULOSE IN SOLUTIONS
© A. S. Shurshina, R. Yu. Lazdin, V. V. Chernova, M. Yu. Lazdina, E. I. Kulish*
Bashkir State University 32 Zaki Validi Street, 450076 Ufa, Republic of Bashkortostan, Russia.
*Email: onlyalena@mail.ru
The influence of low-molecular-weight medicinal substances of electrolytes (amikacin sulfate, cefazolin sodium salt and lidocaine hydrochloride) on the conformational and supramolecular states of the carboxymethyl cellulose sodium salt in solution has been established. It is shown that the introduction of low-molecular-weight salts into the polymer solution is accompanied by a decrease in the characteristic viscosity, an increase in the degree of aggregation of the polymer in solution. In the presence of medicinal substances of electrolytes, there is an earlier formation of a fluctuating net of meshes, an increase in the activation energy of the viscous flow and an earlier transition of the polymer solution to a gel-like state. If the medicinal substance is not an electrolyte, it practically does not affect the conformational-supramolecular state of the polymer in solution.
Keywords: conformation, supramolecular state, characteristic viscosity, rheology, polymer solution.
Introduction
Currently, there is a great need for the development of materials for biomedicine [1-5]. Biocompatible physiologically active polymers of natural origin, mainly polysaccharides, are most often used as the basis for such materials [6-13]. Among them is the sodium salt of carboxymethylcellulose (Na-CMC) [14-19].
Polysaccharide-based materials, including Na-CMC, are most often obtained by processing their solutions. According to it, there are quite a lot of works devoted to Na-CMC solutions. They describe in detail the methods of chemical modification of the polymer by low-molecular-weight compounds [20], mechanical effects on the polymer and its mixtures with other pol-ysaccharides [21], rheological studies of solutions of this polymer [22-24].
However, the difficulty of obtaining materials for biomedicine based on Na-CMC is that in solution this polymer is a polyelectrolyte, whose properties differ from those of nonionic polymers. For example, the conformational state of polyelectrolytes, in addition to temperature, the chemical nature of polymers and solvents, is largely determined by the chemical nature and concentration of low-molecular-weight electrolytes that may be present in the solution. Since medicinal substances used in the process of creating materials for biomedicine are quite often low-molecular-weight salts, the polymer's polyelectrolyte nature can affect its conformational and supramolecular states and, as a consequence, the properties of materials obtained from solutions. It is possible to judge the conformational and supramolecular states of polymers in a solution by its viscous or rheological characteristics [25-27].
Unfortunately, the number of works that take into account the polyelectrolyte nature of polymers in the process of creating materials is small. In this regard,
the aim of this work was to establish the effect of low-molecular-weight medicinal substances of both electrolyte and non-electrolyte nature on the conformational and supramolecular states of Na-CMC in solution in a wide range of concentrations.
Three low-molecular-weight electrolytes were used as a medicinal substance: amikacin sulfate (AMS), cefazolin sodium salt (CFZ), lidocaine hydro-chloride (LD) and non-electrolyte dioxidin (DO).
Experimental
The sodium salt of carboxymethylcellulose with a degree of substitution y = 70% and with molecular weight 260 000 Da, pH = 7.2 was used. Distilled water served as a solvent for CMC. The concentration of CMC in the solution varied from 0.1 to 5 g/dl. The current characteristic viscosity was defined using Ubelode viscometer and calculated using the Bara-nov's method [28], which makes it possible to exclude the influence of the polyelectrolyte swelling effect on the intrinsic viscosity. To determine the aggregation index of polymers, the theory described in detail in the work [29] was used. Any deviation of the indicator 5 = 1.00 evidences that this system is structured. Rheological studies were carried out on a HaakeMarsIII modular dynamic rheometer at 25 °C in the shear deformation mode.
As medicinal substances, amikacin sulfate (AMS) produced by Sintez OJSC (Kurgan, Russia), cefazolin sodium salt (CFZ) produced by Biosynthesis OJSC (Penza, Russia), lidocaine hydrochloride (LD) - by Biochemist PJSC (Saransk, Russia), and dioxidin (DO) - by Novosibkhimpharm OJSC (Novosibirsk, Russia) were used.
Medicinal substances were used without additional purification.
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Results and discussion
It is possible to influence the conformational and supramolecular states of Na-CMC solutions in different ways, for example, by increasing the concentration of the polymer in solution. At the same time, the following changes take place. Firstly, as it can be seen from fig. 1a, with an increase in the content of Na-CMC, there is a decrease in the values of the "current" characteristic viscosity due to the compression of macromo-lecular tangles. This fact indicates the change in the conformational state of the polymer in solution. Secondly, with an increase in the content of Na-CMC, there is an increase in the degree of aggregation of the polymer in solution, which indicates the change in supramolecular state of the polymer. At the same time, the polymer's viscosity begins to depend on the polymer's concentration not according to a linear law, as it does in case of dilute solutions of non-interacting mac-romolecular tangles, but according to a power law 77 ~ C, where 1,00 (fig. 1b).
As a consequence of the interaction between mac-romolecules with an increase in the concentration of
a)
Na-CMC in solution, there is the formation of a fluctuating net of meshes at the concentration of Ce, which is easy to determine by the beginning of a sharp increase in viscosity (curve 1 jig. 2a) and increasing activation energy values (curve 1 jig. 2b).
Another way to influence the conformational-supramolecular state of the polymer in solution, if it is a polyelectrolyte, is the introduction of low-molecular salts (in our case, medicinal compounds) in the polymer solution. As it can be seen from curves 2-4 of fig. 1, the introduction of medical substance (MS), in the case that they are low-molecular-weight electrolytes, significantly affects both the conformational and supramolecular states of the polymer in solution. Thus, the addition of AMS, MS, and CFZ to the solution of ionogenic Na-CMC results in a more significant drop in the characteristic viscosity and a more pronounced increase in the degree of aggregation of the polymer in solution compared with the solution of an individual polymer. At the same time, the more MS is introduced quantitatively, the stronger the observed effect (fig. 3).
b)
Fig. 1. Dependence of the "current" characteristic viscosity value (a) and the degree of aggregation (b) of the Na-CMC solution on the concentration in the absence (1) and presence (2-5) of the medicinal substance AMS (2), LD (3), CFZ (4), and DO (5) taken at a concentration of 0.1 mol/mol of the polymer.
a) b)
Fig. 2. Concentration dependence of complex viscosity (a) and activation energy of viscous flow (b) for Na-CMC solutions in the absence (1) and presence (2-5) of medicinal substances AM (2), CFZ (3), LD (4), and DO (5) taken at a concentration of 0.1 mol/mol polymer.
а)
b)
Fig. 3. Dependence of the characteristic viscosity (a) and the degree of aggregation (b) of Na-CMC solution with a concentration of 1 g/dl, on the ratio MS:polymer when used as MS AMS (1), LD (2), CFZ (3), and DO (4).
а)
b)
fee
3,0
2,0
1,0
-0,5
-1,0
In
/ 2
/ 0.4 0,6 0,8 1,0
Igc
Fig. 4. Dependence of the storage modulus (1) and loss modulus (2) on the content of Na-CMC in solution in the absence (a) and presence of 0.1 mol of AMS (b).
At the same time, the introduction of DO (curves 5 of fig. 1) does not lead to an additional change in the values of current characteristic viscosity and the degree of polymer's aggregation in solution compared with the solution of an individual polymer with corresponding concentration.
Obviously, it is the nature of the MS (electrolyte or non-electrolyte) that plays a fundamental role in determining the solution properties. In the case of the non-electrolytic nature of MS (dioxidine), there are practically no changes in the values of characteristic viscosity and the degree of aggregation compared to individual polymers.
Moreover, the nature of MS affects the values of dynamic (complex) viscosity and activation energy. In the presence of MS electrolytes, a break in the concentration dependence of the complex viscosity, indicating a change in the mechanism of mass transfer in solution, occurs at lower values (curves 2-4 fig. 2a) than for the Na-CMC -
water system (curve 1 fig. 2a) and Na-CMC - water -DO (curve 5 fig. 2a). Consequently, the introduction of MS low-molecular electrolytes results in an earlier formation of net of meshes, which is also characterized by greater strength (fig. 2b).
The values of the storage and loss modulus are also undergoing changes. As in fig. 4a, for example, the dependence of the storage and loss modulus on the concentration of Na-CMC in solution in the absence (fig. 4a) and presence of MS electrolyte (fig. 4b) is shown. It can be seen that, firstly, the values of the storage and loss modulus are greater than in the absence of MS. Secondly, the transition to a gel-like state, in which there is a loss of the ability of the solution to flow, does not occur at a concentration of 3 g/dl, as in the absence of MS, but somewhat earlier (1.5 g/dl).
Thus, due to the fact that Na-CMC is a polyelec-trolyte, the addition of drugs representing low-molecular electrolytes to the polymer solution in a
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wide concentration range is accompanied by changes in the conformational and supramolecular states of the polymer. It can be argued that medicinal substances are actually modifiers of the polymer matrix, which cannot affect 17. some properties of materials formed from solutions. ^
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Received 10.02.2022 г.
