Fate and biocompatibility of three types of microspheres implanted into the brain.

The implantation of polymer devices in the brain that release neuroactive drugs locally and in a controlled manner is gaining increasing interest. The fates and tissue reactions of poly(epsilon-caprolactone), ethylcellulose, and polystyrene microspheres, prepared by the solvent evaporation method, radiosterilized by gamma-irradiation, and stereotactically implanted in rat brain have been studied by routine staining and immunohistochemistry. During the first few days after implantation, a nonspecific astrocytic brain tissue reaction was observed along with a macrophagous-microglial cell reaction typically found following any damage in the central nervous system, except in the presence of certain foreign body giant cells. Nine months into the experiment, microspheres appeared to be engulfed by histiocytic cells. The microsphere cluster was surrounded by a sheath composed of collagen and astrocytic cells. No necrosis was observed, suggesting the absence of toxicity. In some animals, however, an hydrocephalus developed as a result of obstruction of the medial ventricle by some microspheres.

[1]  Thomas We,et al.  Brain macrophages: questions of origin and interrelationship. , 1988 .

[2]  Henry Brem,et al.  Drug Delivery to the Central Nervous System: A Review , 1992 .

[3]  J. Lawrence,et al.  Visualization of migration of transplanted astrocytes using polystyrene microspheres , 1988, Brain Research.

[4]  J. Benoit,et al.  Formation and characterization of cisplatin loaded poly(d,l-lactide) microspheres for chemoembolization. , 1986, Journal of pharmaceutical sciences.

[5]  R. Tamargo,et al.  Interstitial chemotherapy of the 9L gliosarcoma: controlled release polymers for drug delivery in the brain. , 1993, Cancer research.

[6]  T J Ebner,et al.  Sustained release of nerve growth factor from biodegradable polymer microspheres. , 1992, Neurosurgery.

[7]  T. Robinson,et al.  Sustained behavioral recovery from unilateral nigrostriatal damage produced by the controlled release of dopamine from a silicone polymer pellet placed into the denervated striatum , 1990, Brain Research.

[8]  D. Long,et al.  Interstitial delivery of dexamethasone in the brain for the reduction of peritumoral edema. , 1991, Journal of neurosurgery.

[9]  P. Tresco,et al.  An encapsulated dopamine-releasing polymer alleviates experimental parkinsonism in rats , 1989, Experimental Neurology.

[10]  A. Friedman,et al.  Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas. , 1991, Journal of neurosurgery.

[11]  A. Brandwood,et al.  Phagocytosis of carbon particles by macrophages in vitro. , 1992, Biomaterials.

[12]  J. Hilton,et al.  Polymeric controlled release of dexamethasone in normal rat brain , 1991 .

[13]  J. Benoit,et al.  Biodegradation and brain tissue reaction to poly(D,L-lactide-co-glycolide) microspheres. , 1993, Biomaterials.

[14]  R. Tamargo,et al.  The intracerebral distribution of BCNU delivered by surgically implanted biodegradable polymers. , 1992, Journal of neurosurgery.

[15]  J. Koleske,et al.  Lactone Polymerization and Polymer Properties , 1972 .

[16]  Cavanagh Jb,et al.  The proliferation of astrocytes around a needle wound in the rat brain. , 1970 .

[17]  A. Burkhalter,et al.  Fluorescent latex microspheres as a retrograde neuronal marker for in vivo and in vitro studies of visual cortex , 1984, Nature.

[18]  A Deutch,et al.  Controlled release of dopamine from a polymeric brain implant: In vivo characterization , 1989, Annals of neurology.

[19]  R. Tamargo,et al.  Controlled delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea from ethylene-vinyl acetate copolymer. , 1989, Cancer research.

[20]  P. Aebischer,et al.  NGF released from a polymer matrix prevents loss of ChAT expression in basal forebrain neurons following a fimbria-fornix lesion , 1990, Experimental Neurology.

[21]  H. Handa,et al.  [Treatment of brain tumors with anticancer pellet--experimental and clinical study (author's transl)]. , 1982, No shinkei geka. Neurological surgery.

[22]  R. Bleier,et al.  Supraependymal cells of hypothalamic third ventricle: identification as resident phagocytes of the brain. , 1975, Science.

[23]  A. Schindler,et al.  Sustained drug delivery systems II: Factors affecting release rates from poly(epsilon-caprolactone) and related biodegradable polyesters. , 1979, Journal of pharmaceutical sciences.

[24]  Ludwin Sk Reaction of oligodendrocytes and astrocytes to trauma and implantation. A combined autoradiographic and immunohistochemical study. , 1985 .

[25]  T. Tohyama,et al.  [Treatment of malignant brain tumors with slowly releasing anticancer drug-polymer composites]. , 1986, No shinkei geka. Neurological surgery.

[26]  J. Benoit,et al.  A Study of Poly(α-hydroxy acid)s Monolayers Spread at the Air/Water Interface: Influence of the D,L-Lactic Acid/Glycolic Acid Ratio , 1993 .

[27]  H. Brem,et al.  Polymers to treat brain tumours. , 1990, Biomaterials.

[28]  S S Stensaas,et al.  The reaction of the cerebral cortex to chronically implanted plastic needles. , 1976, Acta neuropathologica.

[29]  D. Mason,et al.  Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. , 1986, Immunology.

[30]  A. Cuello,et al.  Microencapsulated monosialoganglioside GM1: physical properties and in vivo effects. , 1989, Journal of microencapsulation.

[31]  H. Winn,et al.  Intracerebral drug delivery in rats with lesion-induced memory deficits. , 1989, Journal of neurosurgery.

[32]  D. Schiffer,et al.  Glial fibrillary acidic protein and vimentin in the experimental glial reaction of the rat brain , 1986, Brain Research.

[33]  R L Schultz,et al.  The ultrastructure of the sheath around chronically implanted electrodes in brain , 1976, Journal of neurocytology.

[34]  S. Hjorth,et al.  Implantable microencapsulated dopamine (DA): A new approach for slow-release DA delivery into brain tissue , 1988, Neuroscience Letters.