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Acta Biomater. 2012 Jul;8(7):2670-87. doi: 10.1016/j.actbio.2012.03.048. Epub 2012 Apr 4.

Antiglioma activity of curcumin-loaded lipid nanoparticles and its enhanced bioavailability in brain tissue for effective glioblastoma therapy.

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1
Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar, Orissa, India.

Abstract

Glioblastoma, the most aggressive form of brain and central nervous system tumours, is characterized by high rates proliferation, migration and invasion. The major road block in the delivery of drugs to the brain is the blood-brain barrier, along with the expression of various multi-drug resistance (MDR) proteins that cause the efflux of a wide range of chemotherapeutic drugs. Curcumin, a herbal drug, is known to inhibit cellular proliferation, migration and invasion and induce apoptosis of glioma cells. It also has the potential to modulate MDR in glioma cells. However, the greatest challenge in the administration of curcumin stems from its low bioavailability and high rate of metabolism. To circumvent the above pitfalls of curcumin we have developed curcumin-loaded glyceryl monooleate (GMO) nanoparticles (NP) coated with the surfactant Pluronic F-68 and vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for brain delivery. We demonstrated that our curcumin-loaded NPs inhibit cellular proliferation, migration and invasion along with a higher percentage of cell cycle arrest and telomerase inhibition, thus leading to a greater percentage apoptotic cell death in glioma cells compared with native curcumin. An in vivo study demonstrated enhanced bioavailability of curcumin in blood serum and brain tissue when delivered by curcumin-loaded GMO NPs compared with native curcumin in a rat model. Thus, curcumin-loaded GMO NPs can be used as an effective delivery system to overcome the challenges of drug delivery to the brain, providing a new approach to glioblastoma therapy.

PMID:
22484149
DOI:
10.1016/j.actbio.2012.03.048
[Indexed for MEDLINE]

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