Targeted drug delivery for brain cancer using a carborane mimic of a cholesteryl este
Peacock, Regina Flinn
MetadataShow full item record
A new cholesterol-carborane conjugate (BCH) has been synthesized as a potential targeting agent for boron neutron capture therapy (BNCT) of cancers. The compound is extremely water-insoluble and was formulated in two liposomal formulations. The liposomal BCH was incubated with 9L rat glioma cells and two human glioblastoma multiforme cell lines, SF-767 and SF-763 to determine if glioma cells in culture could adequately take up the compound. Several factors were evaluated, such as concentration of BCH in the incubation medium, cell confluence, incubation time, and the addition of PEG phospholipids to the liposome formulation. In addition, experiments were conducted in the human glioma cell lines to evaluate the retention of the compound in the cells and the effect of lipoproteins in the incubation media on cell uptake of liposomal BCH. The rat 9L glioma cell uptake studies indicated that the average cellular uptake of BCH in the conventional and PEG liposomal formulations was 49.1 and 45.9 µg boron/ g cells, respectively. Therefore, this compound, formulated in both liposomal formulations, delivered sufficient levels of boron to rat cancer cells in vitro. The compound was further studied in the human glioma cell lines and the data indicate that the amount of BCH taken up increases proportionally with the amount of BCH in the incubation media. The average uptake of boron, at the highest incubation concentration, was 264 ± 36.48 ug boron/ g cells and 283 ± 38.88 µg boron/ g cells in the SF-767 and SF-763 cells, respectively. At 24 hours post-exposure to BCH, ~96% and ~92% were retained in the SF-763 and SF-767 cells, respectively. Both the cell lines appear to take up the BCH very well from this liposome formulation and the BCH seems to circumvent any efflux mechanism that may be present. The data also indicate that lipoproteins in the media affect the cell uptake of liposomal BCH when incubated with SF-767 cells but not with the SF-763 cells. The uptake observed in these experiments was well above the amount required for boron neutron capture therapy (BNCT), which is 20 ug/g cells.