Nanoemulsion formulations for brain tumour therapy

Kadam, Alisha Naresh (2013) Nanoemulsion formulations for brain tumour therapy. Masters thesis, University of Central Lancashire.

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Patients with malignant glioma have poor prognosis in spite of the advances in cancer therapy. Only 15% of the glioma patients survive more than five years after diagnosis. This is because the drug cannot reach the tumour site in sufficient amounts.

The aim of this project is to investigate the hypothesis that nanoemulsion formulations play an effective role as drug-delivery vehicles for the treatment of glioma. Two commercially available nanoemulsion formulations (Clinoleic TPN 20% and Intralipid TPN 20%) were used in this experiment. They were first characterised based on their size, zeta potential, pH and storage stability. Paclitaxel was used as the anti-cancer agent and the methods of loading efficiency determination (via spectrophotometry analysis) and Tissue culture were utilised to measure the effect of the formulation on glioma cell lines (U87-MG- grade IV and SVGP12 - normal glial cells).

Droplet size of the Clinoleic emulsion was increased from 254.1 nm to 264.7 nm when paclitaxel (6 mg/ml) was loaded into the formulation compared to drug-free formulation. Similarly with the Intralipid, the measured size was 283.3 nm and upon inclusion of 6mg/ml paclitaxel the size increased to 294.6 nm. The Polydispersity Index (PDI) of all the nanoemulsion formulations (Clinoleic and Intralipid) were lower than 0.2 irrespective of paclitaxel concentration indicating that all nanoemulsion formulations used were homogenous. The pH values for the Clinoleic formulations (7.1-7.5) were slightly higher (i.e. formulation’s basicity was higher) than those of the Intralipid formulations (6.5-6.9). The Zeta Potential of Clinoleic has a greater negative value than that of Intralipid. The values for Intralipid are closer to neutral. When stored at 4̊ C and room temperature for two weeks major changes were observed in the characteristics of Intralipid formulations, but the Clinoleic formulations remained stable at both temperatures.

In the Clinoleic formulations 70.4 - 80.2% loading efficiencies were observed for paclitaxel. Conversely, lower loading efficiencies were obtained for the Intralipid formulations, being 44.2 – 57.38 %. Clinoleic loaded with paclitaxel successfully decreased the U87-MG cell viability to 6.4 ± 2.3 %, while Intralipid loaded with paclitaxel lowered the cell viability to 21.29 ± 3.82%. On the other hand, both nanoemulsions are less toxic to the normal glial cells (SVG-P12), decreasing the cell viability to 25-35%. This study suggests that nanoemulsions are useful and potentially applicable vehicles of paclitaxel for treatment of glioma

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