Intracranial drug-delivery scaffolds: biocompatibility evaluation of sucrose acetate isobutyrate gels.
BACKGROUND
Sucrose acetate isobutyrate (SAIB) is a water insoluble, biodegradable gel used for controlled-release oral and subcutaneous drug delivery. We investigated SAIB compatibility in the rat central nervous system (CNS) by implanting solutions of SAIB in adult and in neonatal brains.


METHODS
10-15 microL solutions of SAIB gels in 0-30% ethanol were injected into the cerebral cortex of adult Fischer 344 rats. Control animals were implanted with a 10 mg biodegradable poly anhydride copolymer of poly [bis (p-carboxyphenoxy) propane] anhydride and sebacic acid (PCPP:SA). Adult rats were evaluated for signs of pain and distress, including changes in posture, facial signs, and grooming behavior. 1-2 microL solutions of SAIB gels in 15% ethanol were injected into brains of 12-24 h-old rats. Neonatal rats were evaluated for survival. Adult and neonatal brains were examined by histopathology 3-48 days after implant.


RESULTS
Gel implants produced elliptical compression of cortical tissue, cell loss, and inflammation. Cell loss appeared to be confined to the implantation wound and associated neuronal fields. In adult rats, neurophil compression, inflammation, and cell loss appeared similar with the 10-mg PCPP:SA implants and the 10-mg SAIB implants. There was no clinical evidence of pain or distress from SAIB implants. 1-2 microL implants of SAIB-15% ethanol had no effect on survival of neonatal animals.


CONCLUSIONS
Brain implants of SAIB induce a mild to moderate inflammatory response and associated neuronal cell damage. The implants appeared to be biocompatible in adult and neonatal animals. These results suggest that further studies of SAIB as an injectable drug-delivery scaffold for CNS therapeutic agents are warranted.
Lee
James
J
School of Medicine and Department of Neurosurgery, Johns Hopkins University, 817 Hunterian, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Jallo
George I
GI
Penno
Margaret B
MB
Gabrielson
Kathleen L
KL
Young
G David
GD
Johnson
Randolph M
RM
Gillis
Edward M
EM
Rampersaud
Charles
C
Carson
Benjamin S
BS
Guarnieri
Michael
M
D000818:Animals; D001672:Biocompatible Materials; D001921:Brain / Q000187:drug effects; D004343:Drug Implants; D005782:Gels; D051381:Rats; D013395:Sucrose / Q000031:analogs & derivatives* / Q000737:chemistry
D001672:Biocompatible Materials; D004343:Drug Implants; D005782:Gels; D013395:Sucrose; C002885:sucrose acetate isobutyrate