Intracranial drug-delivery scaffolds

Biocompatibility evaluation of sucrose acetate isobutyrate gels

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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)64-70
Number of pages7
JournalToxicology and Applied Pharmacology
Volume215
Issue number1
DOIs
StatePublished - Aug 15 2006

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Scaffolds (biology)
Drug delivery
Biocompatibility
Gels
Rats
Pharmaceutical Preparations
Anhydrides
Brain
Newborn Animals
Propane
Animals
Ethanol
Neurology
sucrose acetate isobutyrate
Central Nervous System Agents
Inflammation
Pain
Grooming
Inbred F344 Rats
Posture

Keywords

  • Biodegradable Scaffold
  • CNS Pharmacology
  • Local Therapy
  • Neonatal
  • Neurotoxicity
  • SAIB
  • Sustained release

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Intracranial drug-delivery scaffolds : Biocompatibility evaluation of sucrose acetate isobutyrate gels. / Lee, James; Jallo, George; Penno, Margaret B.; Gabrielson, Kathleen L; Young, G. David; Johnson, Randolph M.; Gillis, Edward M.; Rampersaud, Charles; Solomon, Benjamin; Guarnieri, Michael.

In: Toxicology and Applied Pharmacology, Vol. 215, No. 1, 15.08.2006, p. 64-70.

Research output: Contribution to journalArticle

Lee, James ; Jallo, George ; Penno, Margaret B. ; Gabrielson, Kathleen L ; Young, G. David ; Johnson, Randolph M. ; Gillis, Edward M. ; Rampersaud, Charles ; Solomon, Benjamin ; Guarnieri, Michael. / Intracranial drug-delivery scaffolds : Biocompatibility evaluation of sucrose acetate isobutyrate gels. In: Toxicology and Applied Pharmacology. 2006 ; Vol. 215, No. 1. pp. 64-70.
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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.",
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AU - Lee, James

AU - Jallo, George

AU - Penno, Margaret B.

AU - Gabrielson, Kathleen L

AU - Young, G. David

AU - Johnson, Randolph M.

AU - Gillis, Edward M.

AU - Rampersaud, Charles

AU - Solomon, Benjamin

AU - Guarnieri, Michael

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