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Review
. 2022 Aug 23;14(17):3442.
doi: 10.3390/polym14173442.

Hyaluronic Acid: A Review of the Drug Delivery Capabilities of This Naturally Occurring Polysaccharide

Ciara Buckley  1   2 , Emma J Murphy  1   3 , Therese R Montgomery  4 , Ian Major  1
Affiliations
Review

Hyaluronic Acid: A Review of the Drug Delivery Capabilities of This Naturally Occurring Polysaccharide

Ciara Buckley et al. Polymers (Basel). .

Abstract

The inclusion of physiologically active molecules into a naturally occurring polymer matrix can improve the degradation, absorption, and release profile of the drug, thus boosting the therapeutic impact and potentially even reducing the frequency of administration. The human body produces significant amounts of polysaccharide hyaluronic acid, which boasts exceptional biocompatibility, biodegradability, and one-of-a-kind physicochemical features. In this review, we will examine the clinical trials currently utilizing hyaluronic acid and address the bright future of this versatile polymer, as well as summarize the numerous applications of hyaluronic acid in drug delivery and immunomodulation.

Keywords: bioactives; drug-delivery; heteropolysaccharides; immunotherapies; naturally-occurring polymers; polysaccharide.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of a disaccharide of HA.
Figure 2
Figure 2
Molecular weight-dependent applications of HA.
Figure 3
Figure 3
The correspondence between RHAMM and CD44 following HA binding affects physiological and cellular functions. The track denoted in green highlights extracellular signaling involving CD44-HA mediated pathways. The blue track is for intracellular RHAMM signaling. Cell surface RHAMM interacts with CD44, HA, and growth factor receptors (GFR) to activate protein tyrosine kinase signaling cascades that activate the ERK1/2 MAP kinase cascade in a c-Src/FAK/ERK1/2 dependent manner (depicted in green track). In the absence of intracellular RHAMM, this signaling can stimulate the transcription of mitogenic effectors to regulate a mitogenic response (cell proliferation/random motility). In the presence of intracellular RHAMM (blue track), MEK-1/p-ERK1/2 also binds to a number of protein partners that allows activated RHAMM to enter the nucleus to regulate functions of microtubule dynamics via centrosome structure/function, and cell cycle progression. Activated RHAMM also controls the expression of genes involved in cell motility. Overall, the effect of HA is pro-proliferation and the development of cellular infrastructure whilst providing critical immune support.
Figure 4
Figure 4
Microbial synthesis of hyaluronic acid in Streptococcus.
Figure 5
Figure 5
Animal synthesis of HA.
Figure 6
Figure 6
Conjugation and crosslinking of HA.
Figure 7
Figure 7
A typical scheme for amidation reaction of HA.
Figure 8
Figure 8
Esterification of HA via glycidyl methacrylate.
Figure 9
Figure 9
Some of the many applications which utilize hyaluronic acid or HA derivatives.
See this image and copyright information in PMC

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