Biocompatibility of poly (DL-lactide-co-glycolide) microspheres implanted into the brain

The delivery of therapeutic molecules to the brain has been limited in part due to the presence of the blood-brain barrier. One potential solution is the implantation of biodegradable polymers with sustained release of drugs. Poly (DL-lactide-co-glycolide) (PLG) is a bioerodible polymer with a long and successful history of use as a suture material. More recently, PLG has been investigated for localized and sustained delivery of molecules into bo th peripheral sites and the brain. Despite its well-defined safety profile for parenteral applications, little information exists concerning the safet y of PLG when implanted into the brain. To further characterize the biocomp atibility of PLG in the brain, we examined the gliotic response following i mplants of PLG into the brains of rats. As a control, each animal received an injection of the suspension medium into the contralateral hemisphere. Fo llowing implantation, PLG was well tolerated. GFAP-positive astrocytes were observed throughout the cerebral cortex and striatum on both the implanted and control sides, with the reaction being greatest within the heavily mye linated fiber tracts of the corpus callosum. Quantitative analyses revealed that this reaction occurred within 1 h postsurgery, reached its peak at 1 week following surgery, and then decreased markedly by 1 month postsurgery. A minimal gliotic reaction was still present 1 year postsurgery but was lo calized to the needle tract. No differences in GFAP reactivity were seen be tween the polymer-implanted and control sides at any time point. Histologic al analysis determined that the majority of the PLG disappeared between 1 a nd 4 weeks. A set of parallel studies in which PLG samples were retrieved f rom the brain at various time points corroborated these findings and determ ined that the majority of PLG degraded within 2 weeks following implantatio n. Together, these results demonstrate that PLG is well tolerated following implantation into the CNS and that the astrocytic response to PLG is large ly a consequence of the mechanical trauma that occurs during surgery. The b iocompatibility of PLG implanted into the CNS provides further support for its use in a wide range of new therapeutic applications for sustained and l ocalized drug delivery to the brain.