A local drug delivery system based on sustained drug release is an attractive approach to treat
brain tumors. We have developed a novel device using
drug-incorporated
poly(lactic-co-glycolic acid) (PLGA)
microspheres embedded in thermoreversible gelation
polymer (TGP) formulation (
drug/PLGA/TGP formulation). TGP forms a gel at body temperature but
sol at room temperature. Therefore, when this formulation is injected into the
brain tumor, the PLGA
microspheres in TGP gel are localized at the injection site and do not diffuse throughout the brain tissue; eventually, sustained drug release from PLGA
microspheres is achieved at the target site. In this study, two chemotherapeutic drugs (
camptothecin (
CPT) or
vincristine (VCR)) were incorporated into PLGA
microspheres to prepare
drug/PLGA/TGP formulations. VCR/PLGA
microspheres exhibited the higher encapsulation efficiency than
CPT/PLGA
microspheres (70.1% versus 30.1%). In addition, VCR/PLGA
microspheres showed a higher sustained release profile than
CPT/PLGA
microspheres (54.5% versus 72.5% release, at 28 days).
Therapeutic effect (mean survival) was evaluated in the C6 rat
glioma model (control group, 18 days;
CPT/PLGA/TGP treatment group, 24 days; VCR/PLGA/TGP treatment group, 33 days). In particular, the VCR/PLGA/TGP formulation produced long-term survivors (>60 days). Therefore, this formulation can be therapeutically effective formulation for the
glioma therapy.