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Nanoparticulate Drug Delivery Systems for the Non-Invasive Chemotherapy of Brain Tumors

S. Gelperina
Russian Research Center of Molecular Diagnostics and Therapy, RU

Keywords:
Cancer, therapy, drug delivery, nanoparticles, non invasive

Abstract:
Effectiveness of the chemotherapy of brain pathologies is often impeded by insufficient drug delivery across the blood-brain barrier (BBB).  The routine approaches applied for the enhancement of drug concentrations in the brain are highly invasive. One of the attractive and innovative alternatives is the non-invasive systemic drug delivery to the brain by means of the nanoparticles.  The authors of the technology provided the experimental evidence that poly(butyl cyanoacrylate) nanoparticles coated with polysorbate 80 enabled efficient brain delivery of the antitumor antibiotic doxorubicin, which is unable to cross the BBB in a free form. Evaluation of the therapeutic potential of this formulation in rats with intracranial glioblastoma demonstrated its high efficacy: the nanoparticle-bound doxorubicin was able to produce long-term remission in >20% animals, whereas in the control group all animals died within 20 days. The surviving animals were euthanized after 3 months and showed no signs of tumor growth at necropsy. The toxicological studies of the nanoparticle-bound doxorubicin provided evidence that this formulation is characterized by a significantly improved toxicological profile, being considerably less toxic for heart and testes. Further studies demonstrated that this technology could be extended to the nanoparticles made of commercially available pharmaceutical polymers, such as poly(lactide-co-glycolide). These important and potentially highly useful results may open up totally novel possibilities for the treatment of diseases of the central nervous system including brain tumors, meningitis of various etiology, Alzheimer's, Parkinson, cerebral AIDS, and other neurological diseases. The technology is patented.

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