Hydrogels on the Base of Modified Chitosan and Hyaluronic Acid Mix as Polymer Matrices for Cytostatics Delivery.

Sergey Kolesov,Alexander Lobov,Leonid Spirikhin,Regina Vildanova

doi:10.3390/gels8020104

Abstract

The development of biodegradable polysaccharide hydrogel matrices for cytostatic delivery can improve the therapeutic results of patients by prolonging the action of the drug, reducing its toxicity and providing additional biological activity by polysaccharides. In this work, N-succinyl chitosan/hyaluronic acid dialdehyde/cytostatic formulations have been prepared using two different chitosan grades (30 kDa and 150 kDa) and hyaluronic acid dialdehyde. The interaction of amino groups of N-succinyl chitosan and aldehydes of hyaluronic acid resulted in the formation of azomethine bonds and was demonstrated using 13C NMR. The elastic properties of the obtained hydrogels determine their use as implants. Two cytostatics—5-fluorouracil and mitomycin C were chosen as drugs because of their using both in oncology and in ophthalmology for the surgical treatment of glaucoma. Hydrogel formulations containing cytostatic were prepared and drug release was studied using in vitro dialysis method. It was established that the molecular weight of N-succinyl chitosan and rheological properties of hydrogel influenced the drug release behavior of the gelling delivery system. Formulations prepared from N-succinyl chitosan with greatest molecular weight and mitomycin C were found to be the most promising for medical application due to their rheological properties and prolonged drug release. Mild preparation conditions, simplicity of the technique, short gelation time (within a minute), 100% yield of hydrogel, suitability for drug release applications are the main advantages of the obtained hydrogels.

Highlights

Hydrogel represent three-dimensional network structure, consisting of chemically or physically cross-linked polymers, holding large amounts of liquid in its meshes
It is known [11], that native chitosan does not dissolve in water, which is some obstacle for the preparation of hydrogels in a neutral medium
It is not possible to significantly increase the number of amino units in N-succinyl chitosan, since in this case the product will not dissolve in water

Summary

Introduction

Hydrogel represent three-dimensional network structure, consisting of chemically or physically cross-linked polymers, holding large amounts of liquid in its meshes. Their unique properties, including high water absorption, tunable mechanical features and sensitivity to various stimuli has made them important candidates in biomedical applications including drug delivery. The use of natural polymers, such as chitosan and hyaluronic acid, allows the transfer of bioactive properties of polysaccharides to the polymer matrix: biodegradability, biocompatibility, mucoadhesiveness, antibacterial and anti-inflammatory properties In terms of their microstructure, hydrogels are similar to the intercellular matrix of many tissues and are capable of imitating its physicochemical properties. They are an ideal cellular microenvironment for cell proliferation and differentiation [7–12]

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Results

Conclusion