Synthesis and characterization of thiolated hexanoyl glycol chitosan as a mucoadhesive thermogelling polymer

Ik Sung Cho,Bo Seul Jang,Kyoung Hwan Park,Sun-Woong Kang,Myeong Ok Cho,Hye Min Oh,Jung-Kyo Cho,Kang Moo Huh

doi:10.1186/s40824-018-0137-7

Abstract

BackgroundMucoadhesive polymers, which may increase the contact time between the polymer and the tissue, have been widely investigated for pharmaceutical formulations. In this study, we developed a new polysaccharide-based mucoadhesive polymer with thermogelling properties.MethodsHexanoyl glycol chitosan (HGC), a new thermogelling polymer, was synthesized by the chemical modification of glycol chitosan using hexanoic anhydride. The HGC was further modified to include thiol groups to improve the mucoadhesive property of thermogelling HGC. The degree of thiolation of the thiolated HGCs (SH-HGCs) was controlled in the range of 5–10% by adjusting the feed molar ratio. The structure of the chemically modified polymers was characterized by 1H NMR and ATR-FTIR. The sol-gel transition, mucoadhesiveness, and biocompatibility of the polymers were determined by a tube inverting method, rheological measurements, and in vitro cytotoxicity tests, respectively.ResultsThe aqueous solution (4 wt%) of HGC with approximately 33% substitution showed a sol-gel transition temperature of approximately 41 °C. SH-HGCs demonstrated lower sol-gel transition temperatures (34 ± 1 and 31 ± 1 °С) compared to that of HGC due to the introduction of thiol groups. Rheological studies of aqueous mixture solutions of SH-HGCs and mucin showed that SH-HGCs had stronger mucoadhesiveness than HGC due to the interaction between the thiol groups of SH-HGCs and mucin. Additionally, we confirmed that the thermogelling properties might improve the mucoadhesive force of polymers. Several in vitro cytotoxicity tests showed that SH-HGCs showed little toxicity at concentrations of 0.1–1.0 wt%, indicating good biocompatibility of the polymers.ConclusionsThe resultant thiolated hexanoyl glycol chitosans may play a crucial role in mucoadhesive applications in biomedical areas.

Highlights

Mucoadhesive polymers, which may increase the contact time between the polymer and the tissue, have been widely investigated for pharmaceutical formulations
Various SH-Hexanoyl glycol chitosan (HGC) with different degrees of thiolation were synthesized from glycol chitosan using a two-step reaction procedure under mild conditions (Fig. 1)
In the first step of the reaction, the amino groups of glycol chitosan were reacted with hexanoic anhydride to form HGC

Summary

Introduction

Mucoadhesive polymers, which may increase the contact time between the polymer and the tissue, have been widely investigated for pharmaceutical formulations. Most typical thermogelling polymers, such as PEG/ PPG and PEG/PLA block copolymers, demonstrate poor bioadhesion and low physical stability they require a high concentration of polymer for thermogelation, limiting their practical application as mucoadhesive formulations. To overcome their limitations, Yuan et al developed a rectal gel formulation based on a mixture of poloxamer 407 and sodium alginate/hydroxypropyl methylcellulose (HPMC) as a thermogelling component and a mucoadhesive component, respectively [8]. Since the polymer alone cannot demonstrate any thermosensitivity, the chemical modification and the additional use of salts or additives such as α,β-glycerophosphate (α,β-GP) were needed for thermogelation

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