An optimized two-vial formulation lipid nanoemulsion of paclitaxel for targeted delivery to tumor

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 110nm (TPLE-1), 220nm (TPLE-2) and 380nm (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 AUC_0-∞ value, smaller plasma clearance (CL), longer mean residence time (MRT) and elimination half-life (T_1/2) 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.