B. Arica et al., Biodegradable bromocryptine mesylate microspheres prepared by a solvent evaporation technique II. Suitability for brain and hypophysis delivery, STP PHARM S, 9(5), 1999, pp. 447-455
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.