In Vitro and Ex Vivo Investigations on the Tolerance and Safety of a 3 kDa Sodium Hyaluronate for Topical Application

(1) Background: Low-molecular-weight hyaluronic acid displays moisturizing and anti-aging properties and reduces UV-induced inflammation when applied topically. A 3 kDa sodium hyaluronate oligosaccharide (Extra-Low HA) was designed, and studies were performed to evaluate its safety for cosmetic applications. (2) Methods: The ability of the Extra-Low HA (ExLMW-HA) to penetrate skin was evaluated. Then, pro-inflammatory cytokines were quantified in the culture medium of skin explants following ExLMW-HA application with or without inflammation inducer (PMA). Finally, four predictive in vitro tests (Keratinosens™, kDPRA, Ames’ test, micronucleus test) were conducted to assess the safety of ExLMW-HA. (3) Results: The molecule permeates skin down to the living epidermis and possibly interacts with the dermal compartment. The oligosaccharide did not induce TNF-α, IL-1β, IL-1α, CXCL2, CCL3, or IL-15, neither in basal nor in stressed conditions. ExLMW-HA is not predicted to be a skin sensitizer or a mutagenic or genotoxic substance. (4) Conclusions: This 3 kDA HA is considered safe for use in topical application at the tested dosage.