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Int J Toxicol. 2009 Jul-Aug;28(4 Suppl):5-67. doi: 10.1177/1091581809337738.

Final report of the safety assessment of hyaluronic acid, potassium hyaluronate, and sodium hyaluronate.

Abstract

Hyaluronic acid, sodium hyaluronate, and potassium hyaluronate function in cosmetics as skin conditioning agents at concentrations up to 2%. Hyaluronic acid, primarily obtained from bacterial fermentation and rooster combs, does penetrate to the dermis. Hyaluronic acid was not toxic in a wide range of acute animal toxicity studies, over several species and with different exposure routes. Hyaluronic acid was not immunogenic, nor was it a sensitizer in animal studies. Hyaluronic acid was not a reproductive or developmental toxicant. Hyaluronic acid was not genotoxic. Hyaluronic acid likely does not play a causal role in cancer metastasis; rather, increased expression of hyaluronic acid genes may be a consequence of metastatic growth. Widespread clinical use of hyaluronic acid, primarily by injection, has been free of significant adverse reactions. Hyaluronic acid and its sodium and potassium salts are considered safe for use in cosmetics as described in the safety assessment.

 Download PDF :  http://www.cir-safety.org/ingredients

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M. Farwick, P. Lersch, G. Strutz 

SOFW-Journal | 134 | 11-2008

Low Molecular Weight Hyaluronic Acid:  Its Effects on Epidermal Gene Expression and Skin Ageing

Conclusions : With the results of the present study it was clearly demonstrate that HA offers not only beneficial effects to the skin but also that these effects can be controlled by varying the molecular size. It was found that LMW HA provides better penetration abilities than larger sized HA and, accordingly, influenced the expression of many genes including those contributing to keratinocyte ifferentiation and formation of intercellular tight junction complexes which are reported to be reduced in aged and photodamaged skin. These different molecular properties of high and low MW HA generated different in-vivo effects with pronounced moisturization and elasticity properties shown for high MW HA and marked reduction of wrinkles demonstrated for LMW HA´s. The increased activity at decreasing molecular weight can be explained by the more efficient skin penetration of the smaller HA molecules.These data show for the first time that topical application of LMW HA improves skin functioning and provides anti-aging effects which could be achieved by strengthening its penetration abilities based on decreasing the molecular size.

Download PDF :  /pdf/sofw-hyacare-50.pdf

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ACS Biomater Sci Eng. Author manuscript; available in PMC 2016 Jul 13.

ACS Biomater Sci Eng. 2015 Jul 13; 1(7): 481–493.  Published online 2015 Jun 15. doi:  10.1021/acsbiomaterials.5b00181

PMCID: PMC4533115 , NIHMSID: NIHMS700819

High and low molecular weight hyaluronic acid differentially influence macrophage activation

Jamie E. Rayahin,1 Jason S. Buhrman,1 Yu Zhang,1 Timothy J. Koh,2 and Richard A. Gemeinhart1,3,4

Abstract

Macrophages exhibit phenotypic diversity permitting wide-ranging roles in maintaining physiologic homeostasis. Hyaluronic acid, a major glycosaminoglycan of the extracellular matrix, has been shown to have differential signaling based on its molecular weight. With this in mind, the main objective of this study was to elucidate the role of hyaluronic acid molecular weight on macrophage activation and reprogramming. Changes in macrophage activation were assessed by activation state selective marker measurement, specifically quantitative real time polymerase chain reaction, and cytokine enzyme-linked immunoassays, after macrophage treatment with differing molecular weights of hyaluronic acid under four conditions: the resting state, concurrent with classical activation, and following inflammation involving either classically or alternatively activated macrophages. Regardless of initial polarization state, low molecular weight hyaluronic acid induced a classically activated-like state, confirmed by up-regulation of pro-inflammatory genes, including nos2, tnf, il12b, and cd80, and enhanced secretion of nitric oxide and TNF-α. High molecular weight hyaluronic acid promoted an alternatively activated-like state, confirmed by up regulation of pro-resolving gene transcription, including arg1, il10, and mrc1, and enhanced arginase activity. Overall, our observations suggest that macrophages undergo phenotypic changes dependent on molecular weight of hyaluronan that correspond to either (1) pro-inflammatory response for low molecular weight HA or (2) pro-resolving response for high molecular weight HA. These observations bring significant further understanding of the influence of extracellular matrix polymers, hyaluronic acid in particular, on regulating the inflammatory response of macrophages. This knowledge can be used to guide the design of HA-containing biomaterials to better utilize the natural response to HAs.

Download PDF :  ACS Biomater Sci Eng. 2015 Jul 13; 1(7): 481–493. 

 

 

 

 

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