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. 2022 Jan 14;7(4):3240-3253.
doi: 10.1021/acsomega.1c05149. eCollection 2022 Feb 1.

Preparation and Characterization of ACE2 Receptor Inhibitor-Loaded Chitosan Hydrogels for Nasal Formulation to Reduce the Risk of COVID-19 Viral Infection

Barbara Vörös-Horváth  1 , Pavo Živković  2 , Krisztina Bánfai  3 , Judit Bóvári-Biri  3 , Judit Pongrácz  3 , Gábor Bálint  1 , Szilárd Pál  1 , Aleksandar Széchenyi  1   2
Affiliations

Preparation and Characterization of ACE2 Receptor Inhibitor-Loaded Chitosan Hydrogels for Nasal Formulation to Reduce the Risk of COVID-19 Viral Infection

Barbara Vörös-Horváth et al. ACS Omega. .

Abstract

The COVID-19 virus is spread by pulmonary droplets. Its high infectivity is caused by the high-affinity binding of the viral spike protein to the ACE2 receptors on the surface of respiratory epithelial cell membranes. The proper hydration of nasal mucosa plays an essential role in defense of bacterial and viral infections. Therefore, a nasal formulation, which can moisture the nasal mucosa and contains the ACE2 receptor inhibitor, can reduce the risk of COVID-19 infection. This article presents a systematic study of the preparation of chitosan hydrogels with dicarboxylic acids (malic and glutaric acid) and their detailed characterization (Fourier transform infrared spectroscopy, determination of cross-linking efficiency, rheological studies, thermal analysis, and swelling kinetics). The results confirm that chemically cross-linked chitosan hydrogels can be synthesized using malic or glutaric acid without additives or catalysts. The adsorption capacity of hydrogels for three different ACE2 inhibitors, as APIs, has also been investigated. The API content of hydrogels and their mucoadhesive property can provide an excellent basis to use the hydrogels for the development of a nasal formulation in order to reduce the risk of SARS-CoV 2 infection.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
FTIR spectra of chitosan and two different hydrogels.
Figure 2
Figure 2
Conductometric titration curve for chitosan and the GA C508 chitosan hydrogel.
Figure 3
Figure 3
Flow curves of chitosan hydrogels cross-linked with malic and glutaric acid at different reaction temperatures. The continuous lines represent the upward curves, and the dotted lines represent the downward curves.
Figure 4
Figure 4
Evaluation of thixotropic behavior of different hydrogels using the hysteresis area method.
Figure 5
Figure 5
Time-dependent viscosity of the GA 4024 chitosan hydrogel.
Figure 6
Figure 6
TGA and the derivative curves of chitosan hydrogels cross-linked with malic acid.
Figure 7
Figure 7
TGA and the derivative curves of chitosan hydrogels cross-linked with glutaric acid.
Figure 8
Figure 8
Swelling kinetics of chitosan hydrogels. MA: hydrogels cross-linked with malic acid. GA: hydrogels cross-linked with glutaric acid.
Figure 9
Figure 9
Swelling kinetics of chitosan hydrogels cross-linked with malic acid.
Figure 10
Figure 10
FTIR spectra of the GA 408 hydrogel (HG), emodin, and emodin-loaded GA 408 hydrogel.
Figure 11
Figure 11
FTIR spectra of the GA 408 hydrogel (HG), glycyrrhizic acid, and glycyrrhizic acid-loaded GA 408 hydrogel.
Figure 12
Figure 12
FTIR spectra of the GA 408 hydrogel (HG), baicalin, and baicalin-loaded GA 408 hydrogel.
Figure 13
Figure 13
Glycyrrhizic acid, baicalin, and emodin release profiles from the MA 408 hydrogel. GLIC: glycyrrhizic acid, BA: baicalin, and EM: emodin.
Figure 14
Figure 14
Glycyrrhizic acid, baicalin, and emodin release profiles from GA 508 hydrogel. GLIC: glycyrrhizic acid, BA: baicalin, and EM: emodin.
Figure 15
Figure 15
Results of mucoadhesivity test of API-loaded hydrogels cross-linked with malic acid. EM: emodin. GLY: glycyrrhizic acid. BA: baicalin. The orange columns represent the increment of viscosity caused by the interaction of hydrogels with mucin.
Figure 16
Figure 16
Results of the mucoadhesive test of API-loaded hydrogels cross-linked with glutaric acid. E: emodin. G: glycyrrhizic acid. B: baicalin. The orange columns represent the increment of viscosity caused by the interaction of hydrogels with mucin.
Figure 17
Figure 17
Mucoadhesion profiles of different chitosan hydrogels cross-linked with malic acid determined using the displacement method. E: emodin. G: glycyrrhizic acid. B: baicalin.
Figure 18
Figure 18
Mucoadhesion profiles of different chitosan hydrogels cross-linked with glutaric acid determined using the displacement method. E: emodin. G: glycyrrhizic acid. B: baicalin.
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