Drug-loaded hyaluronic acid hydrogel as a sustained-release regimen with dual effects in early intervention of tendinopathy

Abstract

Resulting from accumulative microtrauma, impaired healing and oxidative stress, tendinopathy is a debilitating and relentlessly deteriorating disease that greatly affects daily function and quality of life. Current therapy usually provides symptomatic relief only. Sufferers undergo repetitive and protracted treatment courses that rarely alter the disease process. We aim to develop a sustained-release regimen with an intrinsic therapeutic effect in tendinopathy treatment, using oxidised hyaluronic acid/adipic acid dihydrazide hydrogel (HA hydrogel) as both the drug carrier and a mitigating agent of symptoms. We show that HA hydrogel can mitigate tendinopathy changes both in vitro (mechanically induced tendinopathy model) and in vivo (collagenase-induced tendinopathy model). A potent anti-oxidative (pigallocatechin gallate) incorporated into HA hydrogel conferred an additional protective effect in both models. The results indicate that when administered early, combined medications targeting different pathogenesis pathways can resolve tendinopathy. Although facilitating the healing process and mitigating oxidative stress are promising therapeutic strategies, the most effective regimen for tendinopathy treatment has to be determined yet. The established experimental model and drug carrier system provide a platform for exploring new therapeutics against this debilitating disease.

Hyaluronic Acid and Controlled Release: A Review

“…They demonstrated that antiadhesive properties of HA films or coatings are indeed ideal for bacterial biofilm formation that inherently provide an antibacterial barrier. Hsiao [74] et al developed a sustained-release HA-based hydrogel targeting tendinopathy treatment. They formulated oxidized HA/adipic acid dihydrazide hydrogel encapsulating a drug.…”

Fabrication of tri-layered electrospun polycaprolactone mats with improved sustained drug release profile

“…To overcome the problem of dissolution and release of poor drug releasing ability, RGD based cationic polymers have also been reported in the literature 13 . Hence, polymeric encapsulations like scaffolds, hydrogels 14 , nano-carriers and micro-carriers are beneficial to overcome the bottleneck of dissolution and controlled release of hydrophobic drugs [15][16][17] . Encapsulation of hydrophobic drugs into nanofibrous PCL, owing to its potential as drug delivery vehicles, enhances dissolution, whereas its hydrophobic property efficiently modulates rate of water diffusion and leaching out of drugs from these fibers, for sustained long term release 18 .…”

From waste to health: sustainable exploitation of grape pomace seed extract to manufacture antioxidant, regenerative and prebiotic nanovesicles within circular economy

“…This ability seems to be related to the increased deformability, which avoid vesicle destruction and the consequent leakage of the payload. Sodium hyaluronate is a naturally occurring polysaccharide with restoration and the healing properties 75 . It is widely used in the design of new delivery systems due to its biofunctionality associated to bioadhesive and viscoelastic properties 76,77 .…”