Polyunsaturated fatty acids (PUFAs) were conjugated to a highly potent second-generation taxoid, SB-T-1214. The resulting PUFA-taxoids (PUFA = DHA, LNA) were encapsulated into oil-in-water nanoemulsions (NEs) using high pressure homogenization method. The size distribution, zeta-potential and morphology were characterized by Zetasizer and TEM. NE-DHA-taxoid-fluorescein was prepared using sonication method and used as an imaging probe to investigate its mechanism of cellular uptake. By labeling the endosome and lysosome, our confocal microscopy images showed the co-localization of the fluorescence probe and endosome/lysosome, indicating that this NE-taxoid probe was internalized via endocytosis. <i>In vitro</i> efficacy against various cancer cell lines was evaluated and we observed comparable or enhanced cytotoxicity of NE-DHA-SB-T-1214 and NE-LNA-SB-T-1214 as compared to that of SB-T-1214. <i>In vivo</i> efficacy studies of NE-PUFA-taxoids against breast (MX-1) and pancreatic (CFPAC-1) tumor xenografts in SCID mice exhibited significant tumor growth suppression or eradication of the tumor without appreciable systemic toxicity. The observed therapeutic efficacy of the NE-formulated PUFA-taxoids should be attributed to the enhanced permeability and retention (EPR) effect. These results demonstrate that the NE-formulation is a highly efficacious and promising tumor-targeted delivery system for PUFA-taxoids.

High efficacious nanoemulsion (NE) formulation of polyunsaturated fatty acid-taxoid conjugates

255th National Meeting (2018)

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