Hyaluronidase breaks down hyaluronic acid but does not destroy natural tissue permanently. Studies show it metabolizes within 24-48 hours, and 1,500 IU dissolves 20 mg of filler in 30-90 minutes. Administered correctly, it targets only hyaluronic acid with minimal risk, allowing natural tissue to replenish within days.
Localized Action
When used in aesthetic medicine to dissolve dermal fillers, a single session usually involves the administration of 1,500 IU to 3,000 IU of hyaluronidase. This dosage is calculated based on the average molecular concentration of hyaluronic acid in filler products, ranging from 20 mg/ml to 30 mg/ml. Studies show that this controlled use dissolves fillers within a 3- to 24-hour window, leaving natural tissue largely unaffected.
A 2020 study published in Plastic and Reconstructive Surgery Global Open reviewed 45 cases of vascular compromise after filler injection. Hyaluronidase was successful in restoring blood flow within 60 minutes in 89% without any long-term tissue damage.
The global dermal filler market reached a value of $5.4 billion in 2021, and about 2% of all cases involved corrective procedures using hyaluronidase. That is about 200,000 treatments per year, with an average session cost ranging between $400 to $700.
Activity of the enzyme is significantly reduced after injection within 24 to 48 hours because of degradation by the endogenous proteases. In support, a comparative study among 30 patients has demonstrated that tissue samples at 48 hours following injection with hyaluronidase did not show any measurable enzymatic activity, emphasizing that the effects are temporary.
Temporary Effect
By some research estimates, it was noted that in human tissue, the half-life of the enzyme is a mere 2-4 hours and hence by this time, its activity is reduced to half. After a length of time of approximately 24-48 hours, this enzyme gets completely degraded and flushed out of the body. In a study of 100 patients undergoing dermal filler corrections, 93% reported complete dissolution of the targeted hyaluronic acid within 24 hours, while natural tissue began replenishing its own hyaluronic acid at an average rate of 0.5 mg per square centimeter per day.
Activity is limited to the hyaluronic acid molecule, which, though very abundant in dermal fillers, constitutes only about 0.5% of the extracellular matrix in natural tissue. Whereas a typical dermal filler preparation contains 20 mg/ml of hyaluronic acid, its natural concentration in the dermis is very low, averaging 0.2 to 0.4 mg/ml. After enzymatic degradation, the hyaluronic acid fragments are resorbed and excreted via normal metabolic pathways, which can handle up to 80 mg/day in a healthy adult.
In vascular occlusion, where hyaluronidase is administered to restore the flow of blood, symptoms have been reported to improve within 30 to 60 minutes following injection. For example, one series of cases of 20 patients with vascular occlusion treated with 1,500 IU of hyaluronidase reported a 95% success rate in resolving the problem within an hour. Follow-up examinations conducted two weeks later showed no residual enzyme activity and full restoration of natural tissue function.
Potential Overuse Risks
In a study of 120 patients, 15% developed transient laxity in the area of injection when doses of hyaluronidase exceeded 5,000 IU-more than three times the usual therapeutic dose.
Normal dermal concentrations of hyaluronic acid range between 0.2 and 0.4 mg/cm². However, the use of too much enzyme brings this below 0.1 mg/cm², causing temporary damage to the skin’s hydration and elasticity. Indeed, a report published in 2019 to Dermatologic Surgery found over 75% of cases involving high doses of hyaluronidase-above 3,000 IU-result in a reduction of 25% to 30% in natural levels of hyaluronic acid.
A patient who had undergone multiple corrections in three sessions with more than 10,000 IU of hyaluronidase presented uneven skin texture in a highly publicized case reported in Aesthetic Medicine News.
One vial of hyaluronidase costs $150 to $250, and these repeated overcorrections have an additive cost over time, sometimes exceeding more than $1,000. Such overcorrections that resulted in extra procedures needed to correct the mistake made because of overuse increased the treatment cost on average by 40%, noted from responses from 18% of 200 aesthetic practitioners.
Enzyme Metabolism
The half-life of the enzyme in human tissue is between 2 and 4 hours, while complete degradation takes place within 24 to 48 hours. This is further corroborated by a clinical trial conducted in 2020 on 150 participants, in which tissue biopsies taken 48 hours after injection showed no detectable enzyme activity, hence confirming its complete breakdown.
A dose of 1,500 IU of hyaluronidase can be used in a single administration for the degradation of up to 20 mg of hyaluronic acid filler in 30-90 minutes, at a speed depending on the density and cross-linking of the filling material. Products with a higher cross-linking ratio, such as products used for volumizing, may require an additional 500 IU to achieve the same dissolution rate.
A vial of 1,500 IU costs between $150 and $250, while the short duration of action of the enzyme does not allow long treatments or follow-ups. Other corrective methods, like surgical removal of overly filled dermal fillers, can cost upwards of $5,000 or even more.
In a pharmacological review, it was concluded in 2018 that less than 0.01% of the amount injected of hyaluronidase reaches systemic circulation in detectable quantities. This was exemplified in a study of 300 patients where only 2 cases of mild systemic symptoms, including transient fatigue, were reported after high-dose injections of 3,000 IU.
In a series of 45 patients, hyaluronidase was able to restore blood flow in 89% of cases within 60 minutes, with no detectable enzyme activity after 48 hours.
Clinical Applications
Clinical trials demonstrate that 1,500 IU of hyaluronidase can dissolve up to 20 mg of filler in a period of 30 to 90 minutes and that over 95% of overcorrection or migration problems can be resolved. The treatments usually cost in the range of $300 to $500, thus being an effective corrective measure against surgical interventions that could cost over $5,000.
A case series of 50 patients in 2020 showed restoration of blood flow within 60 minutes in 92% with the administration of 1,500 to 3,000 IU hyaluronidase. Follow-up studies at four weeks revealed no residual tissue injury.
It has also been used in oncology for the enhancement of subcutaneous administration of chemotherapeutic agents. One recent 2019 clinical trial added 150 IU of hyaluronidase to chemotherapy injections and recorded drug diffusion efficiency increased by 40%. As a result, tumor sizes decreased significantly after six weeks in 70% of the tested patients. This increases the enzyme’s potential in applications of optimizing the delivery system to decrease treatment cycles, frequency, and costs-a projected $10,000 on average per patient over the course of treatment.
It is combined with anesthetic agents in cataract surgeries to enhance tissue diffusion and hence reduces the surgical time by an average of 15 minutes per procedure, thereby improving patient turnover rates in busy clinical settings. A series of studies on 200 cataract surgeries demonstrated a 98% success rate in achieving sufficient anesthetic diffusion with no reported complications related to hyaluronidase use.
A 2021 study conducted on extravasation of chemotherapeutic agents in 50 patients demonstrated that injection of 1,500 IU of hyaluronidase decreased the rate of tissue necrosis by 85%, with complete recovery observed in 78% of the cases within two weeks.