Biocompatibility of a Biodegradable, Controlled-Release Polymer in the Rabbit Brain

Henry Brem, Abraham Kader, Rafael J. Tamargo, Jonathan I. Epstein, Kam W. Leong, Abraham Domb, Robert Langer

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

The biodegradable polyanhydrides are a new class of controlled release polymers developed for the interstitial delivery of drugs to their target site in the brain or other organs over periods ranging from days to years. These polymers can release molecules of any size in a predictable fashion. Their degradation products are non-cytotoxic and biocompatible. The biocompatibility of a biodegradable polyanhydride, the copolymer of poly[bis(p-carboxyphenoxy)propane] anhydride and sebacic acid (PCPP-SA) in a 50:50 formulation, was studied in the rabbit brain. Twenty adult New Zealand White male rabbits underwent implantation of PCPP-SA in a frontal lobe and absorbable gelatin sponge (Gelfoam) in the other frontal lobe. The animals were evaluated daily until the time of sacrifice. Groups of four animals were sacrificed sequentially on post-operative days 1, 3, 7, 21, and 60, and the brains processed for histological evaluation. None of the animals showed behavioral changes or neurological deficits suggestive of toxicity and all that received implants survived to their date of sacrifice. The histological examination showed no significant differences between the tissue reaction from PCPP-SA compared to Gelfoam. The polymers were also tested in the rabbit cornea bioassay and did not induce an inflammatory response. We conclude that PCPP-SA (50:50), a new biodegradable polymeric matrix that can be surgically implanted for the interstitial delivery of drugs in the brain, is biocompatible in the rabbit brain.

Original languageEnglish
Pages (from-to)55-65
Number of pages11
JournalSelective Cancer Therapeutics
Volume5
Issue number2
DOIs
StatePublished - 1989
Externally publishedYes

Funding

FundersFunder number
National Institute of General Medical SciencesR01GM026698
National Institute of Neurological Disorders and StrokeK08NS001058

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