A recombinant human hyaluronidase sustained release gel for the treatment of post-surgical edema.

Abstract

BACKGROUND: Edema commonly accompanies surgical procedures and when excessive, can adversely affect surgical outcomes. The skin extracellular matrix, including one of its primary components, hyaluronan (HA), is a significant barrier to effective drainage of accumulated edematous fluid. Recombinant human hyaluronidase (rHuPH20) is a human hyaluronidase that acts transiently and locally to depolymerize HA. A non-liposomal gel formulation that provides a sustained release of rHuPH20 was tested in vivo in a preclinical murine model of acquired lymphedema. METHODS: Lymphedemic mice were injected 24 hours before surgery, and at 2 and 12 days following surgery with rHuPH20 sustained release gel (PH20 SR gel). Quantitative assessment of treatment response indicated that a single dose of PH20 SR gel resulted in accelerated resolution and reduced severity of post-surgical edema as compared to the gel vehicle (control). RESULTS: Statistically significant enzymatic degradation of HA was demonstrated up to 5 mm from the injection site, and histological analysis confirmed removal of HA up to 72 hours following PH20 SR gel administration. CONCLUSIONS: These results demonstrate sustained hyaluronidase enzymatic activity that promotes diffusion of accumulated post-surgical edematous fluid, suggesting that PH20 SR gel may be a useful adjuvant in promoting postoperative edema resolution.