GLUTARALDEHYDE CROSS-LINKED CHITOSAN MICROSPHERES AS A LONG-ACTING BIODEGRADABLE DRUG-DELIVERY VEHICLE - STUDIES ON THE IN-VITRO RELEASE OFMITOXANTRONE AND IN-VIVO DEGRADATION OF MICROSPHERES IN RAT MUSCLE
Sr. Jameela et A. Jayakrishnan, GLUTARALDEHYDE CROSS-LINKED CHITOSAN MICROSPHERES AS A LONG-ACTING BIODEGRADABLE DRUG-DELIVERY VEHICLE - STUDIES ON THE IN-VITRO RELEASE OFMITOXANTRONE AND IN-VIVO DEGRADATION OF MICROSPHERES IN RAT MUSCLE, Biomaterials, 16(10), 1995, pp. 769-775
Chitosan microspheres were prepared from 74% deacetylated chitin by th
e glutaraldehyde crosslinking of an aqueous acetic acid dispersion of
chitosan in a mixture of liquid paraffin and petroleum ether stabilize
d using sorbitan sesquioleate as the surfactant. Cross-linking and har
dening of the spherical particles were achieved by the addition of glu
taraldehyde-saturated toluene through the organic phase. A relatively
novel antineoplastic agent, mitoxantrone, was incorporated into the mi
crospheres and the drug release was studied in vitro into phosphate bu
ffer for over 4 weeks at 27 degrees C. Drug release was found to be ef
fectively controlled by the extent of cross-linking. Only about 25% of
the incorporated drug was released over 36 days from microspheres of
high cross-linking density. Implantation of placebo chitosan microsphe
res in the skeletal muscle of rats was carried out in order to assess
the biocompatibility and biodegradability of the microspheres. Histolo
gical analysis showed that the microspheres were well tolerated by the
living tissue. However, no significant biodegradation of the material
was noticed over a period of 3 months in the skeletal muscle of rats.
Data obtained indicate the possibility of using cross-linked chitosan
microspheres as a drug carrier for sustained drug release for very lo
ng periods.