Hyaluronidases: Biological features and current therapeutic applications

Hyaluronidases are enzymes that are able to degrade hyaluronic acid. They are classified into three groups: mammalian, leech and microbial hyaluronidases. Their role in vivo is essential for the homeostasis and metabolism of the extracellular matrix, thus regulating cell growth. Their action can be measured by chemical, physicochemical and biological methods. The first employs reductimetric reactions on the products of hyaluronidases. Physicochemical procedures measure the changes of physical features of the substrate, such asviscosity. Biological methods evaluate the spreading effect of the enzyme in the animal model. Several applications have been described in the literature, mainly as asspreading factor. The most important application is hypodermoclysis, the capacity of increasing absorption and dispersion of an injected drug. Hyaluronidases are used in radiography for increasing the spread of radiopaque substances, in gynecology along with ergometrine to prevent post-partum haemorrhage, in obstretric blocks of the pudendal and ileoinguinal nerve. In ophtalmology, hyaluronidases are instilled with local anesthetics for retrobulbar, peribulbar, sub-Tenon's, and van Lint blocks. In fact, injecting hyaluronidase leads to smaller increases in intraocular pressure (IOP), results in less distortion of the surgical site, decreased incidence of postoperative strabismus, and has the potential for limiting local anesthetic myotoxicity. Hyaluronidase can also be used for post-operative edema reduction. Hyaluronidases are thus employed in transplant surgery to reduce interstitial edema and the risk of rejection. In chemotherapy hyaluronidases prevent the risk of local injury after drug extravasation. In pain therapy the enzymes are employed to increase the spread of local anesthetics in selective blocks, while in cardiology they can reduce myocardial infarction size after coronary occlusion. Moreover hyaluronidases can be successfully used to treat complications arising from inappropriate subcutaneous injection of hyaluronic acid for aesthetic purposes. In fact an excessive inoculation of hyaluronic acid filler may result invisible overcorrection, nodules, bumps or ischemic complications due to compression of the dermal plexus. Given the importance of these enzymes for homeostasis and their applications in medicine, a sound knowledge is essential for everyday practice.