Lipid nanocarrier-based transport of docetaxel across the blood brain barrier

摘要

Successful treatment of brain cancer remains a formidable challenge in neuroscience research due to sub-therapeutic permeation of conventional chemotherapeutics across the blood-brain barrier (BBB). By optimizing various conditions and process parameters, we developed a phospholipid based nanosize carrier (NL) encapsulating docetaxel (DTX) and investigated its BBB crossing potential, both qualitatively and quantitatively, in vivo. The optimized NLs had a nanosize below 100 nm, smooth surface with intact lamellarity, 7.8% drug loading and a sustained drug release profile in vitro. Pharmacokinetic and biodistribution data showed an enhanced residence time of the drug in blood and efficient permeation of the drug from the DTX loaded NL through the BBB, as compared to free DTX. The technetium-99m labeled NL effectively crossed the BBB and accumulated in the brain tissue in a time dependant manner compared to technetium-99m labeled DTX. NL may provide a promising platform for an improved management of brain cancer.