Evaluation of hyaluronic acid gel dissolution with hyaluronidase in an in-vitro prostate cancer model

Highlights • Hyaluronic acid (HA) is an implantable rectum spacer used to decrease rectal radiation dose in prostate cancer radiotherapy. • Hyaluronidase (HAS) is an enzyme that degrades HA, when wrongly positioned. • A ratio of HA:HAS of 1:2 has already a decrease of half of volume on the 2nd day.
Aim To determine a dose response relationship of disintegration of a hyaluronic acid (HA) and hyaluronidase (HAS) used in prostate cancer radiotherapy. Materials and methods Five in-vitro models are applicated with 3 ml (ml) HA. For dissolution varying doses of HAS were used: 6 ml, 3 ml, 1.5 ml, and 0 ml. One ml contains 150 International Units (IU). Each HAS was added with saline till the complementary amount of 6 ml. One phantom was solely implanted with a HA 3 ml acting as a control. Length, width and height were measured on different time points: 1st day 4 times, 2nd day 3 times, third day 2 times, and then once daily during one week, with a final measurement 2 weeks after implantation. The experiments were performed in duplicate to exclude variations and confirm the results. Results The fastest dissolution was observed with the highest concentration of HAS, already observed at the first time point 2 h after implantation, with volume decrease of 50% on the second day, and less than 1 ml residue (33%) on day 4. The 2 other concentrations of HAS also showed a volume decrease, with less than 2 ml (66%) on day 4. All the applied quantities of HAS are observed with a residue of less than 1 ml after 7 days. After 14 days the control phantom and the saline filled one remains on steady state volume (3 ml). Conclusions A dose response was observed by HAS injection: highest volumes of HAS dissolute most swiftly. Using a ratio of HA:HAS of 1:2 results in a decrease to half of initial volume within 24 h. This is of special interest when used in clinical practice following erroneous positioning, and dissolution is urgently needed.