Paclitaxel-loaded cholesterol-conjugated polyoxyethylene sorbitol oleate polymeric micelles for glioblastoma therapy across the blood–brain barrier

Abstract

In this study a brain delivery system was engineered by conjugating cholesterol to polyoxyethylene sorbitol oleate (CPSO) to obtain an amphipathic copolymer that could facilitate the transport of self-assembled CPSO micelles across the blood–brain barrier (BBB). CPSO micelles possessed satisfactory physicochemical properties, such as a mean particle size around 170 nm and a drug loading of ∼20%. It was also proved that CPSO was safe enough for intravenous injections according to the results from the MTT assay, hemolysis rate, vascular stimulation and pathological sections studies. Fluorescent trafficking studies showed that CPSO could significantly accumulate in U87 cells and release payloads in the endolysosomes. Pharmacodynamics studies showed that paclitaxel (PTX)-loaded CPSO micelles could bring about significant tumor inhibitions and prolong the median survival times compared to saline and Taxol® groups. What is more, both in vitro and in vivo results revealed that CPSO exhibited an enhanced capacity to cross the BBB compared to Taxol®. These data indicate that CPSO micelles, a safe and biocompatible drug delivery system, could be a promising carrier candidate for the delivery of chemotherapeutics and/or diagnostics into brain tumors.