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 biodegradable polymeric microspheres using both polymer degradation and protein loading. Biodegradable polymeric microspheres were prepared from PLGA 50/50, PLGA 85/15, PCL and a blend of PCL/PLGA 50/50 (1:1, w/w), where the latter was used to further tailor the degradation rate. The amount of protein loaded in the microspheres was varied, with PCL encapsulating the greatest amount of protein and PLGA 50/50 encapsulating the least. A two-phase release profile was observed for all polymers where the first phase resulted from release of surface proteins and the second phase resulted predominantly from polymer degradation. Polymer degradation influenced the release profile 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-ELISA and PC12 cells, respectively. NGF was found to be bioactive for 91 d, which is longer than previously reported.
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Ontario, Canada.
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D000818:Animals; D001673:Biodegradation, Environmental; D002454:Cell Differentiation / Q000187:drug effects; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D004337:Drug Carriers; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D008863:Microspheres; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000737:chemistry; D009474:Neurons / Q000187:drug effects; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry; D016716:PC12 Cells; D011091:Polyesters; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats
D004337:Drug Carriers; D009414:Nerve Growth Factors; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D010047:Ovalbumin