HEMA/MMMA microcapsule implants in hemiparkinsonian rat brain: biocompatibility assessment using [3H]PK11195 as a marker for gliosis.
Microencapsulation of dopamine-secreting cells in biocompatible, semi-permeable polymer membranes has been proposed as an alternative strategy for dopamine replacement for Parkinson's disease. In order to assess the viability of this proposal, dopamine-secreting PC12 cells were immunoisolated via microencapsulation in a 75:25 2-hydroxyethyl methacrylate/methyl methacrylate (HEMA/MMA) copolymer. A submerged nozzle-liquid jet method was used to produce small diameter (400 microm) microcapsules, which were stereotaxically implanted in the denervated striatum of hemi-Parkinsonian rats. A 96% survival rate was associated with the implantation surgery and no deleterious side effects were apparent. Light microscopy revealed good biocompatibility between the HEMA/MMA copolymer and the host brain, as evidenced by the absence of gross tissue damage at the neuronal tissue/capsule interface. Autoradiographic analyses using [3H]PK11195 as marker for reactive astrocytes revealed a moderate inflammatory response, confined to the immediate vicinity of the injection tract. Quantitative analyses indicated that the local tissue response did not differ significantly between brains implanted with PC12-containing capsules and those implanted with vehicle-containing capsules. Taken together, these results support the biocompatibility of HEMA/MMA copolymer as well as the feasibility and safety of stereotaxic implantation of microcapsules.
Campioni
E G
EG
Department of Pharmacology, University of Toronto, Ont., Canada.
Nobrega
J N
JN
Sefton
M V
MV
D000818:Animals; D001345:Autoradiography; D001672:Biocompatible Materials / Q000633:toxicity*; D001921:Brain / Q000187:drug effects*; D002214:Capsules; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D004298:Dopamine / Q000008:administration & dosage / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005911:Gliosis / Q000139:chemically induced* / Q000175:diagnosis*; D007546:Isoquinolines / Q000378:metabolism; D008297:Male; D008768:Methylmethacrylates / Q000633:toxicity*; D016716:PC12 Cells; D010302:Parkinson Disease, Secondary / Q000188:drug therapy*; D011102:Polyhydroxyethyl Methacrylate / Q000633:toxicity*; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D001672:Biocompatible Materials; D002214:Capsules; D018765:Dopamine Uptake Inhibitors; D007546:Isoquinolines; D008768:Methylmethacrylates; D014316:Tritium; D011102:Polyhydroxyethyl Methacrylate; C040206:HTR composite; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine; D004298:Dopamine; C037850:PK 11195