Morphological characterization of polyanhydride biodegradable implant Gliadel® during in vitro and in vivo erosion using scanning electron microscopy

Wenbin Dang, Todd Daviau, Henry Brem

Research output: Contribution to journalArticle

Abstract

Purpose. The objectives of the current study are to characterize the distribution of the chemotherapeutic agent carmustine (BCNU) in spray dried polyanhydride microspheres and to describe the morphological changes that occur during the in vitro and in vivo erosion of the polyanhydride implant - GLIADEL®, which consists of BCNU distributed in the copolymer matrix of poly(carboxyphenoxy propane:sebacic acid) in a 20:80 molar ratio (p(CPP:SA, 20:80)). Methods. Scanning electron microscopy (SEM) was used to visualize the morphological changes of the polymer during the manufacturing process and in vitro and in vivo erosion. Results. This study revealed that BCNU was homogeneously distributed within spray dried polyanhydride microspheres with no phase separation. The porosity of the wafer fabricated from spray dried polyanhydride microspheres gradually increased during erosion. During the initial period following wafer implantation in the brains of rats, erosion was mainly confined to the surface layer of the wafer with the majority of the wafer remaining intact. The eroding front gradually advanced from the surface to the interior of the wafer in a layerwise fashion, creating pores and connecting channel. Eventually both the interior and exterior of the wafers were eroded and the same porous structure was seen throughout the whole wafer. Conclusions. This study provides the first visual observation of the morphological changes of the GLIADEL® wafer during erosion of the polyanhydride matrix and release of the drug substance BCNU. The observations in this study support the conclusion that BCNU release from a polyanhydride wafer is controlled both by diffusion of the drug and erosion of the polymer matrix.

Original languageEnglish (US)
Pages (from-to)683-691
Number of pages9
JournalPharmaceutical Research
Volume13
Issue number5
DOIs
StatePublished - 1996

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Keywords

  • Biodegradable polymer
  • Brain tumor
  • Controlled release
  • GLIADEL® implant
  • Polyanhydride
  • Scanning electron microscopy

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

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