Study of the Effectiveness of Drugs Based on Molecular Complexes of Adenosine-polymer on the Model of Thermal Burn
Authors: Semivelichenko E. D. , Ermolaeva A. A. , Ponomarenko V. V. , Novoselov A. V. , Plisko G. A. , Ivkin D. Yu. , Antonov V. G. , Karev V. E. , Titovich I. A. , Eremin A. V. 
Published: September 2022

Introduction. In modern pharmacology, more and more widely used molecular complexes (MC) based on donor-acceptor or, on weaker, intermolecular interactions, to stabilize dosage forms in the composition of pharmaceutical substances or their targeted delivery. This trend is actively developing, because the molecules forming MK, which has a certain composition and spatial structure, are preserved and can be released unchanged. The use of MC in tandem with "classical" metal-containing coordination compounds, which enhance or modify the action of the active component, allows the development of new, more effective drugs with optimized bioavailability and activity.

Aim. Evaluation of the wound-healing effect of new substances based on aqueous systems containing coordination compounds of copper(II) or zinc with MC adenosine-copolymer of N-vinylpyrrolidone, in comparison with the drug Depantol® on a model of thermal burn in mice.

Materials and methods. Mononuclear alainate complexes Cu(Ala)2 · H2O and Zn(Ala)2 (Ala – alainate-anion), copolymer of N-vinylpyrrolidone with crotonic acid (PVP-CA) have been synthesized. The composition of the obtained compounds was confirmed by the data of elemental analysis on a CHN (S) analyzer LECO CHNS (O) 932 (Elemental Microanalysis Ltd, Great Britain). IR spectra of the samples were recorded on a IRAffinity-1 (Shimadzu, Japan) instrument (by tabletting a sample with KBr) and a IRTracer-100 (Shimadzu, Japan) instrument equipped with a Specac Quest ATR attachment (Shimadzu Corporation, Japan). Potentiometric titration of the functional groups of the VP copolymer was performed using a PP-20 pH meter (Sartorius AG, Germany). The solutions of the preparations were prepared by dissolving PVP-KK in polyethylene glycol (PEG-400), followed by the addition of an aqueous dispersion of adenosine (Ad) and the corresponding complex of copper(II) or zinc into the preparation. After modeling a thermal burn of the third degree, the overall mortality in the groups and the dynamics of healing of the injured area were assessed. During the experiment, histological studies of areas of damaged tissue after staining of preparations with hematoxylin and eosin were carried out and a generalized scoring assessment of the characteristics of the burn process was carried out, including an assessment of the width and depth of the formed scar tissue, the severity of inflammatory infiltration and the presence of hemosiderosis in the tissues.

Results and discussion. The formation of the MC of the copolymer of N-vinylpyrrolidone with crotonic acid with adenosine made it possible to prepare solutions of preparations containing up to 5 % (wght.) Of the latter. In the obtained samples, the molar ratio of PVP-CA : Ad : M(Ala)2 was 100 : 10 : 1 (M = CuII, Zn), the pH level of the obtained preparations was 7.0–7.1. The resulting funds were applied to the damaged area of the skin in a volume of 0.1 ml/day, each individual, daily for 4 weeks. Introductory substances based on MC PVP-CA : Ad : M(Ala)2 showed a moderate wound healing effect in comparison with the drug Depantol®, based on a water-fat emulsion. Substances that do not contain a metal complex and contain Cu(Ala)2 showed better efficiency in the dynamics of healing a burn injury in comparison with other studied substances, which was combined with a low mortality rate of experimental animals in these groups (3 cases and 2 cases out of 9 individuals, respectively). The reference drug – Depantol®, in turn, showed the best result, probably due to the content in its composition, in addition to dexpanthenol, which is characterized by a wound-healing effect, chlorhexidine antiseptic, and a fatty base, which reduces the dehydration of the injured area.

Conclusion. Experimental substances based on aqueous solutions of adenosine-polymer MK showed a moderate wound healing effect comparable to the reference drug, which, however, is of sufficient interest for further study of such compositions, or their modified versions with the addition of antimicrobial components on thermal burn models, in order to creation of new, more effective drugs for the healing of wound surfaces.