Abstract:
The objective of the current work was to design an injectable, sustained
release formulation of a combination of anticancer drugs, carboplatin
and paclitaxel, for localized delivery. In this combination formulation,
carboplatin was encapsulated into poly(L-lactide) (PLA) microspheres
and paclitaxel was dissolved in thermosensitive biodegradable gel of
PLGA-PEG-PLGA (poly (DL-lactide-co-glycolide- polyethylene
glycol- poly (DL-lactide-co-glycolide)); no external solvent like
cremophorEL was used in the formulation, further, these carboplatin
microspheres were dispersed in the gel containing paclitaxel to achieve
a single delivery system. The combined formulation was assessed for
various parameters for sustained release of both the drugs. Release
profiles of carboplatin from PLA microspheres; paclitaxel from
hydrogel alone and in combination with carboplatin and carboplatin
microspheres dispersed in paclitaxel loaded gel were studied. In vitro
release of both the drugs from PLGA-PEG-PLGA hydrogel showed
that carboplatin was released with 40-50% burst release and paclitaxel
was released in biphasic manner for 50-60 days. Initial burst of
carboplatin was controlled by incorporating it in PLA microspheres
which were then dispersed in paclitaxel loaded hydrogel and the new
formulation did not exhibit any burst release of the drug. Release
pattern of combination formulations revealed that the two drugs were
co-eluting from a single delivery system and the rate of release of each
of the individual drugs was significantly affected.
Thus, a novel injectable combination formulation for sustained and
simultaneous delivery of carboplatin and paclitaxel was developed
which provided sustained release of each of the drugs and could be
further explored in tumor models.