Enzymatic hydrolysis of hyaluronic layer before drug dosing.

Polymeric drug delivery system, allowing the controlled long-term drug release, is a good alternative to the standard way (oral or intravenous) of pharmaceuticals' administration. The most widespread drug release strategy is based on the drug molecules diffusion: first inside the carrier, then through the external layers of carrier and then, outside the carrier, to the cells surrounding. The proposed type of the local therapy is a particularly proper approach in treatment of cancer diseases, at which the drugs are highly toxic. Unfortunately, antitumor drugs diffusion is quite often limited by hyaluronic acid layers abundantly found in a cancer tissue. The undertaken approach assumed relaxation of hyaluronan layer by using a hydrolytic enzyme - hyaluronidase. The considered process corresponds to the heterogenic catalysis with substrate occurred as a layer and a catalyst in a native form. It was shown that enzyme concentration around 4 mg/L kept for 10 minutes in body fluid surrounding HA layers is enough to allow the drug to diffuse. Hydrogel carriers promoting fast release of hyaluronidase were characterized. An expected rate value (the mass transport coefficient app. 4.0.10-7 m/s) was obtained for blends 0.5% κ-carrageenan, 4% polyvinyl alcohol and 0.5% sodium alginate, 6% polyvinyl alcohol.