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Sustained release of acetylcholine in rat hippocampus using a polyanhydride drug‐delivery system
Author(s) -
Mayberg Marc R.,
Gross Alan S.,
Mathiowitz Edith,
Langer Robert
Publication year - 1992
Publication title -
polymers for advanced technologies
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.61
H-Index - 90
eISSN - 1099-1581
pISSN - 1042-7147
DOI - 10.1002/pat.1992.220030608
Subject(s) - parenchyma , hippocampus , acetylcholine , materials science , biodegradable polymer , drug delivery , pharmacology , polymer , medicine , endocrinology , nanotechnology , pathology , composite material
A biodegradable polymer drug‐delivery system has been developed for the selective localized application of agents to brain parenchyma. The copolymer of poly[bis(p‐carboxyphenoxy)propane] anhydride and sebacic acid (PCPP–SA) was impregnated with [ 3 H]‐acetylcholine (ACh) to form 1–5 μm microspheres. Drug‐loaded microspheres were implanted into hippocampus bilaterally in 25 rats, and brain sections processed for autoradiography in groups of five animals at 2, 5, 10, 20 and 40 days, respectively. By densitometric analysis, the concentration of radiolabelled ACh in polymer and adjacent hippocampus rapidly decreased between 2 and 5 days, after which a gradual decrease in [ 3 H]‐ACh was observed up to 40 days. Between 2 and 40 days the concentration of radiolabelled ACh was reduced by 25.8% in polymer matrix and 40.1% in hippocampus. The spread of [ 3 H]‐label into adjacent brain parenchyma showed a similar temporal relationship, with initially wider dispersion at 2 days (44±3 μm), then a linear decrease in dispersion over the remaining period (10±0.9 μxm at 40 days), suggesting bulk flow of the radiolabel into hippocampus. Brain parenchyma showed only a minimal inflammatory reaction to the polyanhydride implants over all time periods. Polyanhydrides can provide localized continuous release of ACh to brain parenchyma, and may potentially be used to deliver various agents to brain in a number of clinical and experimental applications.