Computational studies of mucin 2 and its interactions with thiolated chitosans: a new insight for mucus adhesion and drug retention

Abstract

Chitosans have attracted the interest of the medicinal chemists as mucous adhesive excipients capable of increasing the residence period of drugs inside mucous membranes. Their interactions with the oligomeric mucus gel-forming glycoprotein mucin 2 throughout the intestine determine the level of mucus adhesion, which can be potentiated by the insertion of thiolated substituents on its structure. In this work, we studied the interactions between the mucin 2 and thiolated chitosans, ranking them based on the free energy of receptor–ligand interaction. Results show that when non-bonded interactions were considered, the chitosan-N-acetyl cysteine (AC-Chi) equaled itself in terms of free energy of bonding to the hexamer chitosan-thiobutylamidine (TBA-Chi). The unmodified chitosan (U-Chi) displayed the second greatest ΔG_(binding), showing that the level of mucoadhesion of thiolated chitosans has assumed a diverse order, when considering only the non-binding interactions.

Communicated by Ramaswamy H. Sarma

Keywords:

• Mucin 2
• mucoadhesion
• docking
• thiolated-chitosan
• molecular dynamics
• MM-PBSA

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was funded by Brazilian financial agencies CNPq, grant number [308225/2018-0] and FAPERJ, grant number [E-02/202.961/2017]. This work was supported by the UHK Excellence project.