Abstract
Fillers based on crosslinked hyaluronic acid (HA) are becoming increasingly important in the field of aesthetic medicine, for example for treating wrinkles or for volumizing purposes. However, crosslinking agents are usually associated with toxicity and adverse reactions. The aim of this study is the development of an innovative technology to manufacture high performance HA-based fillers using minimal amounts of crosslinking agent. In this work, new fillers based on HA, functionalized with different amounts of 1,4-butanediol diglycidyl ether (BDDE) (degree of modification ranging between 3.5% and 8.8%) and formulated with a lactose modified chitosan (CTL), were investigated. The relative quantities of these polymeric building blocks in the formulations were 20-25 and 5 mg/mL for HA and CTL, respectively. Due to its cationic nature, CTL could interact with the anionic HA and enhance the elastic properties of the filler. Fillers manufactured with this novel technology (HACL-CTL) were characterized and compared with several fillers available in the market. In particular, resistance against hyaluronidase, swelling, cohesivity and rheological properties were investigated. Cohesivity, resistance to hydrolysis and swelling of HACL-CTL were comparable to commercial products. However, HACL-CTL fillers showed excellent elastic performance that reached 94% of elasticity in response to shear stresses. Surprisingly, these fillers also showed a resistance to compression higher than that of currently marketed products, making them very promising for their lifting effect.