Brain biocompatibility of a biodegradable, controlled-release polymer in rats.
We report the biocompatibility in the rat brain of a controlled-release, biodegradable polymer, the polyanhydride poly-[bis(p-carboxyphenoxy)propane-sebacic acid] copolymer (PCPP-SA) in a 20:80 formulation. The biodegradable polyanhydride can be used for drug delivery directly into the brain, circumventing the difficulties posed by the blood-brain barrier and avoiding the consequences of having to administer toxic doses systematically to reach therapeutic doses in the central nervous system. The tissue reaction in the presence of PCPP-SA was compared to that seen with other standard neurosurgical implants. Fifty-six adult Sprague-Dawley rats were assigned to one of seven groups and underwent bilateral frontal lobe implantation of PCPP-SA (42 hemispheres), Surgicel (oxidized regenerated cellulose) (35 hemispheres), or Gelfoam (absorbable gelatin sponge) (35 hemispheres). None of the animals showed any behavioral changes or neurological deficits suggestive of either systemic or localized toxicity from the biodegradable polyanhydride, all surviving to the scheduled data of sacrifice. PCPP-SA evoked a well localized 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 nontoxic and biocompatible in the rat brain, when compared to standard neurosurgical implants.
Tamargo
R J
RJ
Department of Neurological Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Epstein
J I
JI
Reinhard
C S
CS
Chasin
M
M
Brem
H
H
D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects; D001673:Biodegradation, Environmental; D001921:Brain / Q000378:metabolism*; D004343:Drug Implants / Q000009:adverse effects / Q000378:metabolism*; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008297:Male; D011108:Polymers / Q000009:adverse effects; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001672:Biocompatible Materials; D004343:Drug Implants; D011108:Polymers