A novel animal model for residence time evaluation of injectable hyaluronic acid-based fillers using high-frequency ultrasound-based approach

Abstract

BackgroundHyaluronic acid (HA)-based devices are among the most popular filler agents for skin rejuvenation. One of the principal goals is the improvement in residence time of HA-based products, to increase their performance and reduce frequency of the treatment. So, understanding fillers, behavior after subcutaneous injection is a fundamental aspect for discovery and optimization of new products. Current in vivo approaches to detect/quantify injected HA fillers are not always well optimized or easy to apply.ObjectiveTo develop more efficacious and noninvasive diagnostic tools to make a quantitative evaluation of the degradation of fillers in a small animal model.Materials and methodsWe evaluated the residence time of different HA-based fillers, fluorescein-labeled and not, injected subcutaneously in mice. Volumes of fillers were monitored through high-frequency ultrasound (HF-US) method while fluorescence intensity through the well-established fluorescence living imaging method. To confirm the effectiveness of HF-US, obtained volumetric measurements were compared with fluorescence intensity values.ResultsBoth the presented methods revealed the same degradation kinetics for the tested products.ConclusionThe two used methods are fully comparable and quantitatively accurate. The presented approach has been proved to be noninvasive, sensitive, and reproducible.

Bioactive factors for cartilage repair and regeneration: Improving delivery, retention, and activity

“…Similarly, HA injections show slightly improved results over NSAIDs, and significantly lower the incidence of adverse events and withdrawal [55]. However, residence time of these molecules is a concern, as corticosteroids and HA concentrations diminish rapidly post-injection [56,57], with a residence time of only 6-25 [58,59] and 22-56 days [56,60], respectively. For this reason, intra-articular delivery to maintain therapeutic levels consists of continuous monthly injections [55,61], creating a greater burden on patients with regards to comfort and finances.…”

Towards the prevention of pressure ulcers

“…In agreement with our observation (Fig. 3.17), the hyaluronic acid-based fillers remained in the pocket of the injected region [251].…”

“…To my knowledge, no publication detailed how and where the treatment was administered and whether it will be present in the localised area until recently in 2018 by Merola et al In a novel study by Merola et al, hyaluronic acid-based fillers were injected under the skin para-spinally along the dorsum on each side of the vertebral column [251]. In agreement with our observation (Fig.…”

Hyaluronan and Derivatives: An In Vitro Multilevel Assessment of Their Potential in Viscosupplementation

“…The first and third group products behave more similarly to each other and to natural HA, showing progressive reductions in viscosity during exposure to BTH. In fact, shorter in vivo permanence is expected for the linear HA-based samples [ 10 , 53 , 54 ]. It was remarkable that the diverse macromolecule organization in the third group formula resulted in prolonged retention of rheological performance.…”