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Size matters: differential property of hyaluronan and its fragments in the skin- relation to pharmacokinetics, immune activity and wound healing

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Abstract

Background

Numerous adverse immune reactions after hyaluronan (HA) applications have been reported, highlighting the need for investigating the differences in metabolism and pharmacokinetics between homeostasis and tissue injury and inflammation conditions. Understanding the mechanisms underlying the pro- or anti-inflammatory activity of HA depending on its fragment size and the association between HA fragment size and its pharmacokinetics and therapeutic properties is critical to its use without adverse immune reactions.

Area covered

This paper discusses the differential synthesis and degradation of HA depending on physiological conditions and HA fragment size and the strategies to minimizing adverse immune reactions. Given HA is an important skin component, its skin penetration, dermal pharmacokinetics and differential effects of native HA and fragments on wound healing and tissue regeneration are discussed.

Expert opinion

In ideal homeostatic conditions, the proportion of high-molecular-weight HA (HMW HA; ~106 Da, 1.24 M Da) is high, and it rarely binds with immune cells. However, tissue injury and inflammation lead to the generation of small HA fragments (~ 100 kDa and 10 kDa), which exhibit inflammatory, carcinogenic, and tissue fibrotic properties. As HA is an indispensable extracellular matrix (ECM) component of skin, specific skin absorption enhancement induced by conversion of the α-helix to a ß-sheet structure of HA and hydration of stratum corneum weakens the SC barrier. Given different cell types react differently to cellular stresses. Currently, no general guideline to prognosticating serious adverse reactions after HA application exists. Therefore, we believe that normalization of HA metabolism and an in vitro model evaluating the specific inflammatory cytokine profile and gene expression level in macrophage cell lines of tested tissue after HA exposure would help in devising a clinical strategy to minimize the serious adverse reactions after HA application.

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Acknowledgements

This work was supported in part by the Duksung Women’s University research Grants 2020.

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  1. College of Pharmacy, Duksung Women’s University, 33 Samyangro 144-gil, Dobong-Gu, Seoul, 01369, Korea

    Ae-Ri Cho Lee

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Cho Lee, AR. Size matters: differential property of hyaluronan and its fragments in the skin- relation to pharmacokinetics, immune activity and wound healing. J. Pharm. Investig. 53, 357–376 (2023). https://doi.org/10.1007/s40005-023-00614-1

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