The increasing popularity of hyaluronic acid-based dermal fillers has been accompanied by a growing demand for safe and effective reversal agents. Hyaluronidase, an enzyme that catalyzes the degradation of hyaluronic acid, has emerged as the gold standard for dissolving unwanted or misplaced lip fillers. However, the optimal dose of hyaluronidase remains a subject of clinical debate, influenced by variables such as filler type, volume, injection site, and individual tissue response.

Creative Enzymes is a trusted leader in enzyme supplier. This article is for informational purposes only and provides insights based on current scientific literature and clinical trends. While we highlight general dosing considerations, all aesthetic procedures should be performed under the guidance of qualified healthcare professionals.

Understanding Hyaluronidase and Its Role

Hyaluronidase is a naturally occurring enzyme that plays a vital role in the metabolism of hyaluronic acid (HA)—a key structural molecule found in connective tissue, skin and the extracellular matrix throughout the human body. HA is valued for its remarkable ability to retain water, contributing to skin hydration, plumpness and elasticity. Its gel-like consistency makes it an ideal ingredient for dermal fillers, particularly in aesthetic procedures involving the lips, cheeks and under-eye area.

HA-based dermal fillers are widely used for cosmetic augmentation because of their temporary, reversible nature. However, not all filler applications go as planned. Whether due to overfill, asymmetry, lumpiness, vascular compromise or simply a change of heart, there may come a time when a patient or practitioner wants to reverse the effects of HA-based fillers. That's where hyaluronidase becomes an essential tool in the cosmetic medicine toolbox.

Figure 1. Mechanism of action of hyaluronidase enzyme. (Bala et al., 2017)

Sources and Types of Hyaluronidases

The hyaluronidase used in aesthetic procedures is typically derived from either animal sources (ovine or bovine testicular extracts) or produced via recombinant technology. Recombinant human hyaluronidase has gained popularity due to its reduced risk of allergic reaction, standardized potency, and more predictable performance compared to animal-derived versions.

Figure 2. A summarization of work flow of exploring and exploiting hyaluronidase resources, which contains (A) mining novel hyaluronidases from natural resource or database; (B) decoding novel hyaluronidase sequence, and (C) to realize high level recombinant production of hyaluronidase. (Zhang et al., 2022)

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Factors Influencing Hyaluronidase Dosage

• Type of Filler Used: HA fillers vary in their composition, particularly in terms of cross-linking, which affects their resistance to degradation. Monophasic fillers have a uniform gel consistency, while biphasic fillers consist of HA particles suspended in a gel. Monophasic fillers are generally more resistant to hyaluronidase and may require higher doses for effective dissolution.
• Volume of Filler Injected: The amount of filler present has a direct effect on the hyaluronidase dosage required. A commonly cited guideline is that approximately 5 units of hyaluronidase are required to dissolve 0.1 mL of 20 mg/mL HA filler. However, this may vary depending on the specific filler and individual patient factors.
• Location and Depth of Filler: The anatomical location and depth at which the filler is injected will affect the accessibility of the filler to hyaluronidase. Superficially placed fillers may respond more readily to treatment, while deeper injections may require higher doses or multiple sessions.
• Time Since Filler Injection: Over time, fillers integrate with the surrounding tissue, making them potentially more difficult to dissolve. Older fillers may require increased doses of hyaluronidase or repeated treatments to completely dissolve.

Figure 3. One factor that affects the dosage of hyaluronidase dissolve filler is the location of the filler, which includes forehead lines, under the eyes, nose, cheeks, nasolabial folds, lips. Marionette lines, and chins.

Clinical Guidelines for Hyaluronidase Administration

Dosage Recommendations

Staged Treatments

In many clinical practices, it's common to start low and reassess. This approach—known as stepwise or graded dosing—allows clinicians to:

• Monitor patient response.
• Avoid overcorrection or unintended loss of natural HA.
• Adjust the dose in follow-up sessions (usually spaced 48–72 hours apart).

This conservative approach is especially important in aesthetic areas such as the lips or tear troughs, where excessive dissolution can result in a hollow or uneven appearance.

Injection Technique

Even with the perfect dose, poor technique can compromise results. The method of hyaluronidase delivery is just as important as the amount administered. Here's how experienced practitioners ensure safe and thorough filler breakdown:

Massage for Enhanced Distribution

Once hyaluronidase has been injected, gentle manual massage of the area may

• Facilitate the spread of the enzyme throughout the filler.
• Promote even degradation.
• Prevent localized pooling or incomplete correction.

However, the use of massage must be tailored to the situation - over-massage of inflamed or tender areas can aggravate bruising or swelling and should be approached with caution.

Safety Considerations and Potential Side Effects

• Allergic Reactions: Although rare, allergic reactions to hyaluronidase can occur. Patients with a history of hypersensitivity to bee stings or certain medications should inform their clinician, as they may be at increased risk.
• Over-Dissolution: Excessive hyaluronidase can lead to the breakdown of not only the filler but also the body's natural HA, potentially resulting in volume loss or skin irregularities. Clinicians often adopt a conservative approach, starting with lower doses and reassessing before administering additional enzyme.
• Other Side Effects: Common, usually mild, side effects include swelling, bruising, redness, and tenderness at the injection site.

Post-Treatment Expectations

Patients can expect to see noticeable changes within 24 to 48 hours of hyaluronidase injection. However, complete dissolution may require multiple sessions, especially for larger or more resilient filler deposits. Physicians typically schedule follow-up appointments to assess progress and determine if additional treatment is needed.

In conclusion, hyaluronidase dissolution of lip fillers is a safe and effective procedure when performed by experienced physicians. Determining the appropriate number of units requires a comprehensive assessment of several factors, including filler type and volume, injection depth, and individual patient characteristics. Open communication between patient and physician, coupled with an individualized treatment approach, ensures optimal results and patient satisfaction.

Creative Enzymes offers various high-quality hyaluronidase for your research and industrial applications, contact us today for any inquiries and questions.