Brain biocompatibility of a biodegradable, controlled-release polymer in rats zyx Rafael J. Tamargo,* Jonathan I. Epstein,§ Carla S. Reinhard,* Mark Chasin,’ and Henry Brem,*”,* zyxwvuts Departments zyxwvutsrq of *Neurological Surgery, ‘Ophthalmology, #Oncology, sPatkology, and %Irology, The Johns Hopkins University School zyxwvut of Medicine, and ‘Nova Pharmaceutical Corporation, Baltimore, Maryland We report the biocompatibility in the rat brain of a controlled-release, biodegrad- able polymer, the polyanhydride poly- [bis( zyxwvut p-carboxyphenoxy)propane-sebacic acid] copolymer (PCPP-SA) in a 20: 80 for- mulation. The biodegradable polyanhy- dride can be used for drug delivery directly into the brain, circumventing the diffi- culties posed by the blood-brain barrier and avoiding the consequences of having to administer toxic doses systemically to reach therapeutic doses in the central ner- vous system. The tissue reaction in the presence of PCPP-SA was compared to that seen with other standard neurosur- gical implants. Fifty-six adult Sprague- Dawley rats were assigned to one of seven groups and underwent bilateral frontal lobe implantation of PCPP-SA (42 hemi- spheres), Surgicel (oxidized regenerated cellulose) (35 hemispheres), or Gelfoam (absorbable gelatin sponge) (35 hemi- spheres). None of the animals showed any behavioral changes or neurological deficits suggestive of either systemic or localized toxicity from the biodegradable polyanhy- dride, all surviving to the scheduled data of sacrifice. PCPP-SA evoked a well local- ized inflammatory reaction, comparable to that of Surgicel, which resolved as the PCPP-SA polymer degraded over five weeks. The biodegradable polyanhydride has been shown in this study to be non- toxic and biocompatible in the rat brain, when compared to standard neurosurgical implants. INTRODUCTION We have developed a system for interstitial drug delivery in the brain that circumvents the difficulties posed by the blood-brain barrier (BBB) and avoids the consequences of having to administer toxic doses of drugs sys- temically to reach therapeutic doses in the central nervous system (CNS). This system consists of incorporating drugs into solid biodegradable poly- mers, which can then be surgically implanted in the brain to release the drug locally, in a sustained and controlled fashion, for periods ranging from days to years. Supported in part by the Association for Brain Tumor Research Fellowship in Memory of Steven Lowe, NIH Grant No. NS01058-01, American Cancer Society Grant No. IN- IlW, the Andrew W. Mellon Foundation Johns Hopkins University Faculty Develop- ment Award, and a grant from Nova Pharmaceutical Corporation. Address reprint requests to: Henry Brem, M.D., Department of Neurological Sur- gery, The Johns Hopkins Hospital, Meyer 7-113, 600 North Wolfe Street, Baltimore, MD 21205. Journal of Biomedical Materials Research, Vol. 23, 253-266 (1989) zyx 0 1989 John Wiley & Sons, Inc. CCC 0021-9304/89/020253-14$04.00