Biodegradable bromocryptine mesylate microspheres prepared by a solvent evaporation technique II. Suitability for brain and hypophysis delivery

The purpose of the present work, which is focused on the loading of bromocr yptine mesylate into biodegradable microspheres with the purpose of prolong ing its therapeutic activity, is to study the biodegradation and tissue res ponse after brain and hypophysis tissue implantation. For this purpose, sur gery was performed under aseptic conditions. Sprague-Dawley rats were divid ed into three groups. The rats were anaesthetised with intraperitoneal inje ctions of a ketamine hydrochloride (Ketalar)/xylazine hydrochloride (Romphu n) mixture. They received Either blank poly(L-lactides), poly(D,L-lactides) and poly(D, L-lactidc-co-glycolide) microspheres or bromocryptine mesylate -loaded microspheres ill the brain and hypophysis tissue by intracerebral i mplication, The right hemisphere was used as a control and the left hemisph ere was used as a sample. The rats were sacrificed with all overdose of ana esthetic at 7 days, 14 days and 4 months after the implantation. Histologic al examinations were performed with light microscopy and transmission elect ron microscopy. Blank microspheres showed no inflammatory response or other adverse effects in the rat brain and hypophysis and completely biodegraded after 4 months in vivo. No physical signs of toxicity toxicity were shown by the animals receiving bromocryptine mesylate-loaded microspheres. The ce llular response was characterized by the presence of fibroblast at day 7. A t day 120, the cell reaction was the same as that at day 21. This work: sug gests that bromocryptine mesylate-loaded biodegradable microspheres is poss ibly safe to implant in the mt brain and hypophysis, and that these I,micro spheres carl be used in prolonging bromocryptine mesylate release.