Design, Synthesis, Characterization, and In Vitro Evaluation of a New Cross-Linked Hyaluronic Acid for Pharmaceutical and Cosmetic Applications.

Sabrina Sciabica,Elisa Durini,Stefano Manfredini,Luisa Canilli,Dina M Silva,Larissa Gomes Dos Reis,Daniela Traini,Giovanni Tafuro,Silvia Vertuani,Massimo Terno,Anna Baldisserotto,Alessandra Semenzato

doi:10.3390/pharmaceutics13101672

Abstract

Hyaluronic acid (HA), an excellent biomaterial with unique bio properties, is currently one of the most interesting polymers for many biomedical and cosmetic applications. However, several of its potential benefits are limited as it is rapidly degraded by hyaluronidase enzymes. To improve the half-life and consequently increase performance, native HA has been modified through cross-linking reactions with a natural and biocompatible amino acid, Ornithine, to overcome the potential toxicity commonly associated with traditional linkers. 2-chloro-dimethoxy-1,3,5-triazine/4-methylmorpholine (CDMT/NMM) was used as an activating agent. The new product (HA–Orn) was extensively characterized to confirm the chemical modification, and rheological analysis showed a gel-like profile. In vitro degradation experiments showed an improved resistance profile against enzymatic digestions. Furthermore, in vitro cytotoxicity studies were performed on lung cell lines (Calu-3 and H441), which showed no cytotoxicity.

Highlights

Over the past decade, hyaluronic acid (HA) has proven to be one of the best materials for application in various fields including pharmaceutical, food, and cosmetic applications, mostly due to its safety profile and unique physicochemical, biological, and viscoelastic properties.HA is commonly used in ophthalmology to protect and lubricate the delicate eye tissues, supplement vitreous humour, and in cataract surgery to replace lost vitreous fluid and to maintain the space and avoid the collapse of the eye tissue during the operation
CDMT, in association with NMM, was found to be the most efficient actisynthesis of HA–Orn was carried at room with temperature vator
We designed and synthesized a new hyaluronic acid derivative crossIn summary, we designed and synthesized a new hyaluronic acid derivative crosslinked by an ornithine derivative

Summary

Introduction

Hyaluronic acid (HA) has proven to be one of the best materials for application in various fields including pharmaceutical, food, and cosmetic applications, mostly due to its safety profile and unique physicochemical, biological, and viscoelastic properties.HA is commonly used in ophthalmology to protect and lubricate the delicate eye tissues, supplement vitreous humour, and in cataract surgery to replace lost vitreous fluid and to maintain the space and avoid the collapse of the eye tissue during the operation. Pharmaceutics 2021, 13, 1672 been considered as an appropriate candidate to support skin tissue regeneration It is often included, alone or in combination with other therapeutic agents, in topical formulations for the treatment of skin irritations and wounds including abrasions and burns as well as post-surgical, metabolic, and vascular ulcers. These products are used in the dermatological field and in ophthalmology, otolaryngology rhinology, and dentistry [4]. Biomimetic injectable biogels have been designed and developed via the cohesive molecular assembly of a network of polysaccharide polymers to provide HA with in situ gelling properties and avoid implant surgery [6]

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Conclusion