Novel paclitaxel formulations solubilized by parenteral nutrition nanoemulsions for application against glioma cell lines

• Published in: International journal of pharmaceutics 2016-06, Vol.506 (1-2), p.102-109
• Main Authors: Najlah, Mohammad, Kadam, Alisha, Wan, Ka-Wai, Ahmed, Waqar, Taylor, Kevin M.G., Elhissi, Abdelbary M.A
• Format: Article
• Language: English
• Subjects: Anticancer; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Cell Line, Tumor; Chemistry, Pharmaceutical - methods; Droplet size; Drug Carriers - chemistry; Drug Delivery Systems - methods; Emulsions - administration & dosage; Emulsions - chemistry; Excipients - chemistry; Glioma - drug therapy; Humans; MTT assay; Nanoemulsion; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - chemistry; Parenteral Nutrition - methods; Particle Size; Phospholipids - chemistry; Plant Oils - chemistry; Solubility; Soybean Oil - chemistry; Stability
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.04.027

[Display omitted] The aim of this study is to investigate using nanoemulsion formulations as drug-delivery vehicles of paclitaxel (PX), a poor water-soluble anticancer drug. Two commercially available nanoemulsion fat formulations (Clinoleic 20% and Intralipid 20%) were loaded with PX and characterised based on their size, zeta potential, pH and loading efficiency. The effect of formulation on the cytotoxicity of PX was also evaluated using MTT assay. The droplet size of the Clinoleic emulsion increased from 254.1nm to 264.7nm when paclitaxel (6mg/ml) was loaded into the formulation, compared to the drug-free formulation. Similarly, the droplet size of Intralipid increased from 283.3 to 294.6nm on inclusion of 6mg/ml paclitaxel. The Polydispersity Indexes (PDIs) of all the nanoemulsion formulations (Clinoleic and Intralipid) were less than 0.2 irrespective of paclitaxel concentration indicating that all nanoemulsion formulations used were homogeneously sized. The pH range for the Clinoleic formulations (7.1–7.5) was slightly higher than that of the Intralipid formulations (6.5–6.9). The zeta potential of linoleic had a greater negative value than that of Intralipid. Loading efficiencies for paclitaxel were 70.4–80.2% and 44.2–57.4% for Clinoleic and Intralipid formulations, respectively. Clinoleic loaded with paclitaxel decreased the viability of U87-MG cell to 6.4±2.3%, compared to Intralipid loaded with paclitaxel (21.29±3.82%). Both nanoemulsions were 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.