Hyaluronidase

Not all hyaluronidases are the same. There are three major families of enzymes that break down hyaluronic acid: mammalian hyaluronidases (found in humans and other animals), bacterial lyases (which use a different chemistry), and enzymes from leeches and crustaceans 1. PB3000 belongs to the first family — it uses classical hydrolysis (the same chemistry as most digestive enzymes) to cut hyaluronic acid at very specific spots. It mainly acts on hyaluronic acid, with just a small amount of activity on related sulfated sugars — a very different substrate target than lyase PB72K.

Why recombinant matters. Historically, hyaluronidase used in medicine was extracted from bull or sheep testicles. These preparations work, but they're variable in purity, inconsistent from batch to batch, and carry allergy risks from leftover animal proteins. Recombinant hyaluronidases (like PB3000 and human-sequence rHuPH20) are produced in controlled microbial hosts 2 — resulting in defined, consistent activity and much lower risk of allergic reactions. For topical cosmetic use involving repeated application, this purity is critical for long-term tolerability.

Acts on both natural and injected hyaluronic acid — but with a preference. Hyaluronidase doesn't distinguish between the HA your body naturally makes and HA that was previously injected as a dermal filler — it works on both. In a topical protocol (often facilitated by microneedling to help the enzyme reach the dermis), PB3000 primarily rebalances excess or poorly distributed natural HA in the upper skin layers, rather than completely dissolving deep filler deposits. Cross-linked filler HA (the modified version used in most injectable fillers) is more resistant to the enzyme because the chemical crosslinking hides the cutting sites — so topical application preferentially addresses free, unbound hyaluronic acid rather than aggressively dissolving filler.

Temporary and reversible — by design. Hyaluronidase's action isn't permanent. Studies using recombinant human hyaluronidase show that when it depolymerizes hyaluronic acid in tissue, the HA recovers naturally within about 24 hours 2 — meaning the effect is transient and self-limiting. A separate 8-week clinical trial on topical formulations that modulate both HA synthesis and breakdown showed statistically significant improvements in fine lines, texture, brightness, and hydration 5 — confirming that working with HA balance topically is a meaningful, measurable clinical endpoint.