Indomethacin-loaded nanocapsules treatment reduces in vivo glioblastoma growth in a rat glioma model.
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.
Bernardi
Andressa
A
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Braganhol
Elizandra
E
Jäger
Eliézer
E
Figueiró
Fabrício
F
Edelweiss
Maria Isabel
MI
Pohlmann
Adriana R
AR
Guterres
Sílvia S
SS
Battastini
Ana M O
AM
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000637:transplantation; D003342:Corpus Striatum; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D053769:Nanocapsules / Q000008:administration & dosage*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015173:Supratentorial Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D000077204:Temozolomide; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D053769:Nanocapsules; D003606:Dacarbazine; D007213:Indomethacin; D000077204:Temozolomide