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

James Lee; George I. Jallo; Margaret B. Penno; Kathleen L. Gabrielson; G. David Young; Randolph M. Johnson; Edward M. Gillis; Charles Rampersaud; Benjamin S. Carson; Michael Guarnieri

doi:10.1016/j.taap.2006.02.009

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

James Lee, George I. Jallo, Margaret B. Penno, Kathleen L. Gabrielson, G. David Young, Randolph M. Johnson, Edward M. Gillis, Charles Rampersaud, Benjamin S. Carson, Michael Guarnieri

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

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 μL 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 μL 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 μL 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.

Original language	English (US)
Pages (from-to)	64-70
Number of pages	7
Journal	Toxicology and Applied Pharmacology
Volume	215
Issue number	1
DOIs	https://doi.org/10.1016/j.taap.2006.02.009
State	Published - Aug 15 2006

Keywords

Biodegradable Scaffold
CNS Pharmacology
Local Therapy
Neonatal
Neurotoxicity
SAIB
Sustained release

ASJC Scopus subject areas

Toxicology
Pharmacology

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10.1016/j.taap.2006.02.009

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title = "Intracranial drug-delivery scaffolds: Biocompatibility evaluation of sucrose acetate isobutyrate gels",

abstract = "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 μL 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 μL 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 μL 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.",

keywords = "Biodegradable Scaffold, CNS Pharmacology, Local Therapy, Neonatal, Neurotoxicity, SAIB, Sustained release",

author = "James Lee and Jallo, {George I.} and Penno, {Margaret B.} and Gabrielson, {Kathleen L.} and Young, {G. David} and Johnson, {Randolph M.} and Gillis, {Edward M.} and Charles Rampersaud and Carson, {Benjamin S.} and Michael Guarnieri",

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doi = "10.1016/j.taap.2006.02.009",

language = "English (US)",

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T1 - Intracranial drug-delivery scaffolds

T2 - Biocompatibility evaluation of sucrose acetate isobutyrate gels

AU - Lee, James

AU - Jallo, George I.

AU - Penno, Margaret B.

AU - Gabrielson, Kathleen L.

AU - Young, G. David

AU - Johnson, Randolph M.

AU - Gillis, Edward M.

AU - Rampersaud, Charles

AU - Carson, Benjamin S.

AU - Guarnieri, Michael

PY - 2006/8/15

Y1 - 2006/8/15

N2 - 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 μL 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 μL 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 μL 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.

AB - 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 μL 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 μL 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 μL 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.

KW - Biodegradable Scaffold

KW - CNS Pharmacology

KW - Local Therapy

KW - Neonatal

KW - Neurotoxicity

KW - SAIB

KW - Sustained release

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

Abstract

Keywords

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