The utilization of biodegradable materials for the delivery of bioactive molecules that promote CNS regeneration

Abstract

Growth inhibitory proteins limit axonal regeneration in the injured spinal cord and a common target of these inhibitors is the Rho family of small GTPases. Activation of RhoA leads to growth cone collapse and neurite retraction. An enzyme from Clostridium botulinum, C3 transferase (C3), blocks RhoA function by ADP ribosylation of the effector domain, and this promotes regeneration of injured neurons. The aim of this work was to develop C3-loaded microspheres for implantation in the injured spinal cord. The approach of blending capped (hydrocarbon end-groups) and uncapped (free acid end-groups) poly(D,L-lactide-co-glycolide) (PLGA) to achieve continuous release of C3 was investigated. The microspheres were prepared by w/o/w emulsification and the in vitro release and degradation profile were characterised. Microspheres prepared from capped/uncapped PLGA with a blending ratio of 30/70 yielded continuous, average daily release of 3.0 ng/day/mg of microspheres of C3 in one month. This study demonstrates the feasibility of using PLGA microspheres for sustained delivery of C3.