期刊
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
卷 4, 期 2, 页码 165-173出版社
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2008.014
关键词
oil-in-water nanoemulsion; Microfluidizer (R); chlorambucil; ovarian adenocarcinoma cells; cytotoxicity; apoptotic activity
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(R) M-110EH processor. The optimized nanoemulsion formulations were investigated for cellular uptake, cytotoxicity, and apoptotic activity in SKOV3 human ovarian adenocarcinoma cells. The Microfludizer(R) 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 Microfluiclizer(R) processor. The nanoemulsion formulations were effective in intracellular delivery of chlorambucil, which enhanced the therapeutic effect in tumor cells.
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