Chlorambucil loaded in mesoporous polymeric microspheres
as oral sustained release formulations with enhanced hydrolytic stability
Wang, XY (Wang, Xiuyan)[ 1 ] ; Cao, YY (Cao, Yanyan)[ 1 ] ; Yan, HS (Yan, Husheng)[ 1,2 ]
MATERIALS
SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS, 2018, 91: 564-569
DOI: 10.1016/j.msec.2018.05.078
WOS:000442192000057
Abstract
Chlorambucil,
a chemotherapeutic agent, is usually administered orally to treat chronic
lymphocytic leukemia and some other types of cancers in regimens of
conventional and metronomic chemotherapies. However, the hydrolytic instability
of chlorambucil is a major limitation in achieving the optimum therapeutic
performance. In this work, mesoporous polymeric microspheres were prepared by
free radical suspension copolymerization of methyl acrylate and divinylbenzene
in the presence of porogen. Chlorambucil was loaded into the mesoporous
polymeric microspheres through adsorption of the drug in aqueous media with
high loading capacity up to more than 350 mg/g. Chlorambucil-loaded mesoporous
polymeric microspheres showed sustained release property in media simulating
gastrointestinal fluids, with nearly zero order release kinetics. Furthermore,
the mesoporous polymeric microspheres as carriers greatly stabilized
chlorambucil against its hydrolysis. The hydrolyzation percentage of
Chlorambucil that was adsorbed on the microspheres after incubation for 36 h in
media simulating gastrointestinal fluids was less than 10%, while more than 90%
of free chlorambucil hydrolyzed after incubation in the same media for 4 h. The
chlorambucil-loaded mesoporous polymeric microspheres may be used as oral
sustained release formulations, especially as oral formulations for the
application in metronomic chemotherapy.