NANOMEDICINE FOR EFFICIENT CHEMOTHERAPY OF BRAIN TUMOURS: FROM BENCH TO BEDSIDE
Abstract
The nanoparticle formulation of doxorubicin (DOX-PLGA) was developed as a novel candidate for systemic chemotherapy of glioblastoma. The technology is based on poly(lactide-co-glycolide) (PLGA) nanoparticles coated with poloxamer 188. Following intravenous administration, the nanoparticles acquire a biological surface through adsorption of plasma proteins, including apolipoproteins, which is believed to contribute to their altered biodistribution and improved delivery of doxorubicin to brain tumours. Recent evidence further suggests that interactions with blood cells, particularly erythrocytes, may also contribute to the altered biodistribution of nanoparticles, although the underlying mechanisms remain to be fully elucidated. Preclinical studies demonstrated that DOX-PLGA produced pronounced growth inhibition of intracranially implanted 101.8 glioblastoma in rats and induced long-term remission in more than 20% of animals, whereas the conventional formulation was only marginally effective. Histological examination confirmed the antitumour effect and demonstrated efficient intratumoral penetration and accumulation of the nanoparticles. Importantly, DOX-PLGA also exhibited a favourable toxicological profile, particularly with respect to cardiotoxicity, as demonstrated by both functional and histological evaluation. The reduced toxicity is most likely associated with nanoparticle-mediated changes in drug biodistribution.
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