Brain biocompatibility of a biodegradable controlled release polymer consisting of anhydride copolymer of fatty acid dimer and sebacic acid

Henry Brem, Abraham Domb, Doris Lenartz, Catalino Dureza, Alessandro Olivi, Jonathan I. Epstein

Research output: Contribution to journalArticle

Abstract

The development of new biodegradable polymers (e.g. PCPP-SA) has allowed the prolonged controlled release of lipid soluble chemotherapeutic agents in the laboratory and clinically. In order to optimize this approach, a new polymer has been developed (the copolymer of fatty acid dimer and sebacic acid p[FAD-SA]) to release water soluble agents. In this study we sought to determine the safety and biocompatibility of this new polymer in the brain. We compared the tissue reaction to this polymer to the reaction observed with oxidized cellulose (SurgicelR) and with absorbable gelatin sponge (GelfoamR). Fifty-six adult Fischer 344 rats were assigned to 1 of 7 groups and underwent bilateral 3 mm burr holes. Neurological or behavioral changes were assessed daily and the groups were killed sequentially on postoperative days 3, 6, 10, 15, 21, 28, and 36. No neurological deficits or behavioral changes suggestive of either systemic or localized toxicity were observed in the animals implanted with the new polyanhydride. A well demarcated acute inflammatory response was seen at day 3 and 6 for p(FAD-SA) and SurgicelR implants. The inflammatory response remained well localized and resolved with total degradation of the polymer by day 36. The localized reaction evoked by this polymer was comparable to the one of the previously studied biodegradable polymers (PCPP-SA) and to the response to commonly used surgical hemostatic materials such as SurgicelR. The biodegradable copolymer of fatty acid dimer and sebacic acid may play an important role in drug delivery to the brain by by-passing the blood-brain barrier to administer water soluble agents directly to the brain.

Original languageEnglish (US)
Pages (from-to)325-329
Number of pages5
JournalJournal of Controlled Release
Volume19
Issue number1-3
DOIs
StatePublished - Mar 1992

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Keywords

  • Anticancer drugs
  • Biodegradable polymers
  • Brain biocompatibility

ASJC Scopus subject areas

  • Pharmaceutical Science

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