TPLEs with particle sizes of 110 nm (TPLE-1), 220 nm (TPLE-2) and 380 nm (TPLE-3) were prepared. Consequently, TPLE-1 displayed distinctly higher drug-loading rate, slower PTX-release and a larger PTX distribution in oil phase, greater AUC0-∞ value, longer MRT and T1/2, and could significantly increase tumor-uptake, and showed more potent in vitro and in vivo antitumor efficacy compared to TPLE-2 and TPLE-3. It also exhibited the same in vivo efficacy as Taxol®, and couldn’t cause haematolysis and intravenous irritation response yet. Moreover, its LD50 was 4.3-fold higher than that of Taxol®.
The discovery of new intravenous drug delivery carrier for water-insoluble drug is a challenging task. In this paper, novel two-vial formulation of paclitaxel (PTX)-loaded lipid nanoemulsions (TPLEs) with particle sizes of 110 nm (TPLE-1), 220 nm (TPLE-2) and 380 nm (TPLE-3), which were formed by mixing a PEG400 solution of PTX and 10% (w/w) blank lipid emulsions (BLEs) with different particle size prior to use, were developed and comparatively evaluated for their pharmaceutics, pharmacokinetics, biodistribution, in vitro and in vivo anticancer efficiency. Among them, TPLE-1 displayed higher PTX-loading, slower PTX-release and larger PTX-distribution in oil-phase, significantly reduced extraction by RES organs, increased tumor-uptake, showed stronger cytotoxicity against MCF-7 cells and more potent anticancer efficacy on MCF-7 tumor-bearing nude mice, and had greater plasma AUC0-∞ value, smaller plasma clearance (CL), longer mean residence time (MRT) and elimination half-life (T1/2) in SD rats. It also exhibited the same in vivo efficacy as Taxol® and even produced less hemolysis and intravenous irritation. Moreover, its LD50 was 4.3-fold higher than that of Taxol®. All results demonstrate that TPLE-1 is a promising candidate drug due to its high tumor-accumulation and effectiveness, low toxicity, good safety and druggability in clinical application for the cancer therapy.