Thiolated Hyaluronic Acid as Versatile Mucoadhesive Polymer: From the Chemistry Behind to Product Developments—What Are the Capabilities?

Abstract

Within the last decade, intensive research work has been conducted on thiolated hyaluronic acids (HA-SH). By attaching sulfhydryl ligands onto naturally occurring hyaluronic acid various types of HA-SH can be designed. Due the ability of disulfide bond formation within the polymer itself as well as with biological materials, certain properties such as mucoadhesive, gelling, enzyme inhibitory, permeation enhancing and release controlling properties are improved. Besides the application in the field of drug delivery, HA-SH has been investigated as auxiliary material for wound healing. Within this review, the characteristics of novel drug delivery systems based on HA-SH are summarized and the versatility of this polymer for further applications is described by introducing numerous relevant studies in this field.

Emulating Human Tissues and Organs: A Bioprinting Perspective Toward Personalized Medicine

“… 163 It is continuously degraded in vivo by hyaluronidase enzymes, as well as being recognized by cells through CD44 cell surface receptors. 164 Because of its low in vivo stability, HA’s structure is usually modified with different moieties (e.g., (meth)acrylate, thiols) before being used in bioprinting. By doing such modifications, HA is able to participate in cross-linking reactions, yielding constructs with an increased in vivo stability.…”

“…By doing such modifications, HA is able to participate in cross-linking reactions, yielding constructs with an increased in vivo stability. 164 …”

“… 219 , 220 The use of thiolated HA is also reported as a thiol moiety for bioinks. 152 , 222 The thiolation of this polysaccharide can be obtained by different routes as described in a recent review by Griesser et al 164 For example, Yan et al 223 used the thiol-maleimide reaction to promote the reaction of thiolated gelatin with PEG functionalized with two maleimide groups, forming a covalent network with thioether bonds. The bioink was supplemented with laminin-derived amphiphilic fibril-forming peptides that supported the formation of a noncovalent network at 4 °C and improved cellular adhesion.…”

Thiolation of Biopolymers for Developing Drug Delivery Systems with Enhanced Mechanical and Mucoadhesive Properties: A Review

“…Griesser et al reported thiolated hyaluronic acid to be a versatile polymer for drug delivery and biomedical application with improved properties viz. gelling, mucoadhesion, permeation enhancement, enzyme inhibition and controlled/sustained drug release [ 38 ].…”

Attachable Hydrogel Containing Indocyanine Green for Selective Photothermal Therapy against Melanoma

“…Most trials on hydrogels for the treatment of cancer have investigated the injection of hydrogels into mice [ 22 , 23 , 24 ]. A series of injectable and cross-linked hydrogels using biocompatible and carbohydrate-based polymers such as quaternized chitosan, hyaluronic acid, fucoidan, and poly-ethylene glycol have been developed as nanocarriers for the delivery of therapeutic agents [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. However, hydrogels remain in the injection site for a certain period of time, which may promote inflammation and other side effects [ 33 , 34 ].…”