Multimodal combinations of target agents with radiation and
chemotherapy may enhance
cancer treatment efficacy; however, despite these treatments,
gliomas recur early due to their highly proliferative, infiltrative and invasive behaviors. Nanoparticles of biodegradable
polymers for anticancer drug delivery have attracted intensive interest in recent years since they may provide a sustained, controlled and targeted delivery. In the present study, we investigated the effect of
indomethacin-loaded
nanocapsules in an experimental
glioma model. The rats treated with
indomethacin-loaded
nanocapsules demonstrated a significant reduction in
tumor size and half of these animals presented just cells with characteristics of a
residual tumor, as shown by immunostaining for
nestin. Pathological analyses showed that the treated
gliomas presented a significant reduction in the mitotic index and other histological characteristics that indicate a less invasive/proliferative
tumor. An important finding of the present study is that
indomethacin carried by polymeric
nanocapsules achieved higher intracerebral drug concentrations than those of
indomethacin in
solution. Furthermore,
indomethacin achieved a greater concentration in the hemisphere where the
glioma was implanted, compared with the contralateral healthy hemisphere.
Indomethacin-loaded
nanocapsule treatment did not cause characteristics of toxicity and increased the survival of animals. Thus, our results show that polymeric
nanocapsules are able to increase the intratumoral bioavailability of
indomethacin and reduce the growth of implanted
gliomas. Data suggest that
indomethacin-loaded
nanocapsules could offer new and potentially highly effective strategies for the treatment of
malignant gliomas.