A Theoretical Model for Release Dynamics of an Antifungal Agent Covalently Bonded to the Chitosan

Luminita Marin,Stefan-Andrei Irimiciuc,Maricel Agop,Marcel Popa,Decebal Vasincu,Alexandru Anisiei,Tudor-Cristian Petrescu,Loredana Himiniuc

doi:10.3390/molecules26072089

Abstract

The aim of the study was to create a mathematical model useful for monitoring the release of bioactive aldehydes covalently bonded to the chitosan by reversible imine linkage, considered as a polymer–drug system. For this purpose, two hydrogels were prepared by the acid condensation reaction of chitosan with the antifungal 2-formyl-phenyl-boronic acid and their particularities; influencing the release of the antifungal aldehyde by shifting the imination equilibrium to the reagents was considered, i.e., the supramolecular nature of the hydrogels was highlighted by polarized light microscopy, while scanning electron microscopy showed their microporous morphology. Furthermore, the in vitro fungicidal activity was investigated on two fungal strains and the in vitro release curves of the antifungal aldehyde triggered by the pH stimulus were drawn. The theoretical model was developed starting from the hypothesis that the imine-chitosan system, both structurally and functionally, can be assimilated, from a mathematical point of view, with a multifractal object, and its dynamics were analyzed in the framework of the Scale Relativity Theory. Thus, through Riccati-type gauges, two synchronous dynamics, one in the scale space, associated with the fungicidal activity, and the other in the usual space, associated with the antifungal aldehyde release, become operational. Their synchronicity, reducible to the isomorphism of two SL(2R)-type groups, implies, by means of its joint invariant functions, bioactive aldehyde compound release dynamics in the form of “kink–antikink pairs” dynamics of a multifractal type. Finally, the theoretical model was validated through the experimental data.

Highlights

Chitosan is a polysaccharide extensively investigated over the last decades due to its outstanding biologic properties, which make it an excellent candidate for the development of a large variety of biomaterials [1]
The in vitro release of the antifungal aldehyde by shifting the imination equilibrium of the reagents was observed in an acidic medium of pH 4.2 similar to the vagina environment, by monitoring the absorbance of the aldehyde by UV-Vis and fitting it on a previously drawn calibration curve
The paper reports for the first time a theoretical model for the release of a bioactive compounds covalently bonded to a matrix, i.e., on an imine-chitosan system obtained by covalent bonding of an antifungal aldehyde to the chitosan via reversible imine linkages

Summary

Introduction

Chitosan is a polysaccharide extensively investigated over the last decades due to its outstanding biologic properties, which make it an excellent candidate for the development of a large variety of biomaterials [1]. Recent studies demonstrated that the imination reaction of chitosan has a reversibility degree favored by the acidic medium in which chitosan is soluble [3] This finding is in line with well-documented investigations that demonstrated that the imine linkage has a reversible character that proved beneficial for the construction of dynamic materials with an ability to adapt under the influence of various environment stimuli, such as moisture, temperature, pressure or pH [11,12,13]. These recent discoveries opened new perspectives for the use of chitosan as a matrix for the controlled release of the reversible bonded aldehydes [3,14]. This simple mechanism becomes of particular importance when the released aldehyde has bioactive properties and its delivery is controlled by its consumption

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Conclusion