Sustained release of nerve growth factor from biodegradable polymer microspheres.
Although grafted adrenal medullary tissue to the striatum has been used both experimentally and clinically in parkinsonism, there is a definite need to augment long-term survival. Infusion of nerve growth factor (NGF) or implantation of NGF-rich tissue into the area of the graft prolongs survival and induces differentiation into neural-like cells. To provide for prolonged, site-specific delivery of this growth factor to the grafted tissue in a convenient manner, we fabricated biodegradable polymer microspheres of poly(L-lactide)co-glycolide (70:30) containing NGF. Biologically active NGF was released from the microspheres, as assayed by neurite outgrowth in a dorsal root ganglion tissue culture system. Anti-NGF could block this outgrowth. An enzyme-linked immunosorbent assay detected NGF still being released in vitro for longer than 5 weeks. In vivo immunohistochemical studies showed release over a 4.5-week period. This technique should prove useful for incorporating NGF and other growth factors into polymers and delivering proteins and other macromolecules intracerebrally over a prolonged time period. These growth factor-containing polymer microspheres can be used in work aimed at prolonging graft survival, treating experimental Alzheimer's disease, and augmenting peripheral nerve regeneration.
Camarata
P J
PJ
Department of Neurosurgery, University of Minnesota, Minneapolis.
Suryanarayanan
R
R
Turner
D A
DA
Parker
R G
RG
Ebner
T J
TJ
D000313:Adrenal Medulla / Q000637:transplantation; D000818:Animals; D001479:Basal Ganglia; D001673:Biodegradation, Environmental; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid; D008863:Microspheres; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000494:pharmacology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D013268:Stimulation, Chemical; D016042:Transplantation, Heterotopic
D003692:Delayed-Action Preparations; D009414:Nerve Growth Factors; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid