Resorbable alginate embolic microsphere for Musculoskeletal embolization applications

Abstract

Resorbable embolic agents can be used for musculoskeletal (MSK) pain relief applications using a Transarterial Embolisation (TAE) technique. However, inconsistent particle size and shape, degradation rates, and unpredictable resorption and excretion of the breakdown products, limit their widespread clinical adoption. The present study reports self-degradable, rehydratable, freeze-dried, resorbable Ca2+-crosslinked alginate microspheres as a novel vascular embolic agent. The alginate lyase enzyme was incorporated into the alginate microspheres to achieve a controlled degradation rate under physiological conditions. Whilst the feasibility of alginate microspheres as embolic agents has been demonstrated, this is the first study where the controlled release is achieved in physiological conditions. To incorporate the alginate lyase enzyme in the alginate matrix, its activity was reversibly inhibited by preparing an alginate lyase-alginate-excipient mixture in a pH 3.6-3.9 buffered solution. An electrostatic encapsulator enabled the scalable preparation of microspheres of size 210 {+/-} 8 {micro}m at room temperature. The results showed that freeze-dried microspheres regained their shape and size within two minutes after reconstitution with saline, along with active alginate lyase. The reperfusion time of alginate microspheres was evaluated using digital subtraction angiography (DSA) and compared with imipenem and celestine (IMP-CS)in a porcine renal arterial embolisation model. It was observed that most of the blood vessels reperfused within 130-210 minutes, and complete vascular blush was recovered within 24 hours. Embolization with resorbable alginate microspheres induced recoverable ischemic necrosis in the targeted renal arteries. This unique feature of resorbable alginate microspheres in inducing ischemic necrosis, potentially in pain-propagating neovessels, makes it an ideal candidate embolic agent for treating MSK-associated pain using the TAE technique.