A novel injectable-chitosan-based delivery system with low cytotoxicity was
fabricated in the study. The chitosan microspheres with small particle siz
e, low crystallinity and good sphericity were prepared by a spray-drying me
thod followed by treating with a crosslinker. In the study, a naturally occ
urring crosslinking reagent (genipin), which has been used in herbal medici
ne and in the production of food dyes, was used to crosslink the chitosan m
icrospheres. The glutaraldehyde-crosslinked counterparts were used as a con
trol. Histological study of the genipin-crosslinked chitosan microspheres i
njected intramuscularly into the skeletal muscle of a rat model showed a le
ss inflammatory reaction than its glutaraldehyde-crosslinked counterparts.
The results of the scanning electron microscopic examination indicated that
the glutaraldehyde-crosslinked chitosan microspheres retrieved at 12-week
postoperatively were already degraded into a loose and porous structure. Ho
wever, the degradation of the genipin-crosslinked chitosan microspheres was
not significant after 20 weeks of implantation. The results of the study d
emonstrated that the genipin-crosslinked chitosan microspheres have a super
ior biocompatibility and a slower degradation rate than the glutaraldehyde-
crosslinked chitosan microspheres. Accordingly, the genipin-crosslinked chi
tosan microspheres may be a suitable polymeric carrier for long-acting inje
ctable drug delivery. (C) 2001 Elsevier Science Ltd. All rights reserved.