Delivering neuroactive molecules from biodegradable microspheres for application in central nervous system disorders

Nerve growth factor (NGF) may enhance axonal regeneration following injury to the central nervous system (CNS), such as after spinal cord injury. The release profile of NGF, co-encapsulated with ovalbumin, was tailored from b iodegradable polymeric microspheres using both polymer degradation and prot ein loading. Biodegradable polymeric microspheres were prepared from PLGA 5 0/50, PLGA 85/15, PCL and a blend of PCL/PLGA 50/50 (1:1, w/w), where the l atter was used to further tailor the degradation rate. The amount of protei n loaded in the microspheres was varied, with PCL encapsulating the greates t amount of protein and PLGA 50/50 encapsulating the least. A two-phase rel ease profile was observed for all polymers where the first phase resulted f rom release of surface proteins and the second phase resulted predominantly from polymer degradation. Polymer degradation influenced the release profi le most notably from PLGA 50/50 and PLGA 85/15 microspheres. The amount and bioactivity of released NGF was followed over a 91 d period using a NGF-EL ISA and PC12 cells, respectively. NGF was found to be bioactive for 91 d, w hich is longer than previously reported. (C) 1999 Elsevier Science Ltd. All rights reserved.