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Microfluidic Preparation of Chlorambucil Nanoemulsion Formulations and Evaluation of Cytotoxicity and Pro-Apoptotic Activity in Tumor Cells

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The objective of this study was to formulate chlorambucil, a lipophilic DNA alkylating agent, in soybean oil-containing nanoemulsion formulations for improved delivery efficiency in solid tumors. The nanoemulsions were prepared using a high pressure homogenization method with a Microfluidizer® M-110EH processor. The optimized nanoemulsion formulations were investigated for cellular uptake, cytotoxicity, and apoptotic activity in SKOV3 human ovarian adenocarcinoma cells. The Microfludizer® processing conditions were optimized (12,500 psi for 30 sec) to obtain the average oil droplet size below 150 nm in diameter. The control, poly(ethylene glycol) (PEG)-modified, and cationic lipid (i.e., DOTAP)-modified nanoemulsion formulations had excellent chlorambucil encapsulation efficiency (>97%). The cytotoxicity and the pro-apoptotic activity of chlorambucil were significantly enhanced when administered in the nanoemulsion formulations relatively to aqueous solution. The results of this study show that stable oil-in-water nanoemulsion formulations can be prepared with a commercially-available Microfluidizer® processor. The nanoemulsion formulations were effective in intracellular delivery of chlorambucil, which enhanced the therapeutic effect in tumor cells.
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Document Type: Research Article

Publication date: June 1, 2008

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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