Strategies for Hyaluronic Acid-Based Hydrogel Design in Drug Delivery

Abstract

Hyaluronic acid (HA) is a natural, linear, endogenous polysaccharide that plays important physiological and biological roles in the human body. Nowadays, among biopolymers, HA is emerging as an appealing starting material for hydrogels design due to its biocompatibility, native biofunctionality, biodegradability, non-immunogenicity, and versatility. Since HA is not able to form gels alone, chemical modifications, covalent crosslinking, and gelling agents are always needed in order to obtain HA-based hydrogels. Therefore, in the last decade, different strategies for the design of physical and chemical HA hydrogels have been developed, such as click chemistry reactions, enzymatic and disulfide crosslinking, supramolecular assembly via inclusion complexation, and so on. HA-based hydrogels turn out to be versatile platforms, ranging from static to smart and stimuli-responsive systems, and for these reasons, they are widely investigated for biomedical applications like drug delivery, tissue engineering, regenerative medicine, cell therapy, and diagnostics. Furthermore, the overexpression of HA receptors on various tumor cells makes these platforms promising drug delivery systems for targeted cancer therapy. The aim of the present review is to highlight and discuss recent advances made in the last years on the design of chemical and physical HA-based hydrogels and their application for biomedical purposes, in particular, drug delivery. Notable attention is given to HA hydrogel-based drug delivery systems for targeted therapy of cancer and osteoarthritis.

Hydrogel Biomaterials for Application in Ocular Drug Delivery

“…Physical bonding occurs through interactions between the polymer chains such as ionic bonding, Van der Waals forces, hydrogen bonding, or hydrophobic forces. Due to these types of bonds, the hydrogels formed through physical bonds are known to be reversible and have a degree of instability (Trombino et al, 2019). The hydrogels formed through physical interactions are generally less stable than those formed through chemical interaction as these bonds are susceptible to formation and breakage when there are changes in pH, temperature, and ionic strength.…”

“…Chemically formed hydrogels are known as "permanent" hydrogels due to the covalent bonds which form between polymer chains. These systems allow more stability and maintain their structure better than the physical hydrogels (Trombino et al, 2019). However, it is important that the cross-linking agent can be removed completely from the hydrogel or a non-toxic agent is used so as to prevent adverse tissue reactions when the hydrogel is placed into the eye (Hoare and Kohane, 2008).…”

“…and cross-linking or gelling agents. Hyaluronic acid hydrogels have been investigated as a drug delivery system because they are able to be formulated as both static and stimuli-response (Trombino et al, 2019).…”

Injectable Hydrogel-Based Nanocomposites for Cardiovascular Diseases

“…Drug delivery with hydrogel can change the harsh environment of diseased tissue (Hasan et al, 2015). Hydrogels have a highly porous structure in which irregular pores are connected to each other throughout the structure (Trombino et al, 2019), and the drug or a biologically active substance like a liposome-encapsulated alpha-tocopherol (Qu et al, 2019) or Ferulic acid (FA) (Cheng et al, 2016) is uniformly distributed in the porous structure. The inlaid structure of the hydrogel creates a sustained release system to sustained-release to resists oxidative stress inflammatory response and improved cardiomyocyte survival rate.…”

The Application of Hyaluronic Acid-Based Hydrogels in Bone and Cartilage Tissue Engineering

“…e biocompatibility of synthetic polymer hydrogels needs improvement. ere have been several in-depth studies of the natural polymer HA [9][10][11][12][13]. As a constituent of the natural cytoplasmic matrix, favorable biological activity of HA and its ability to communicate with cells are undisputed.…”