Intracranial drug-delivery scaffolds: Biocompatibility evaluation of sucrose acetate isobutyrate gels

Journal Article · Tue Aug 15 00:00:00 EDT 2006 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2006.02.009· OSTI ID:20850394

Lee, James ^[1]; Jallo, George I ^[1]; Penno, Margaret B ^[2]; Gabrielson, Kathleen L ^[3]; Young, G David ^[4]; Johnson, Randolph M ^[5]; Gillis, Edward M ^[5]; Rampersaud, Charles ^[5]; Carson, Benjamin S ^[1]; Guarnieri, Michael ^[1]

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1. School of Medicine and Department of Neurosurgery, Johns Hopkins University, 817 Hunterian, 725 North Wolfe St, Baltimore, MD 21205 (United States)
2. Department of Medicine, Johns Hopkins University, 1017 Blalock, 600 North Wolfe Street, Baltimore, MD 21287 (United States)
3. Department of Comparative Medicine, Johns Hopkins University, 855 Broadway Research Building, 733 North Broadway, Baltimore, MD 21205 (United States)
4. Gene Logic Incorporated, 610 Professional Drive, Gaithersburg, MD 20879 (United States)
5. DURECT Inc., 10240 Bubb Road, Cupertino, CA 95014 (United States)

Introduction: 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 {mu}L 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 {mu}L 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 {mu}L implants of SAIB-15% ethanol had no effect on survival of neonatal animals. Conclusion: 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.

• OSTI ID: 20850394
• Journal Information: Toxicology and Applied Pharmacology, Vol. 215, Issue 1; Other Information: DOI: 10.1016/j.taap.2006.02.009; PII: S0041-008X(06)00074-3; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACETATES
CEREBRAL CORTEX
COPOLYMERS
DRUGS
ETHANOL
GELS
IMPLANTS
INFLAMMATION
PAIN
PHARMACOLOGY
PROPANE
RATS
SACCHAROSE
SEBACIC ACID
THERAPY
WOUNDS