Preparation and Characterization of Paclitaxel Palmitate Albumin Nanoparticles With High Loading Efficacy: an in Vitro and in Vivo Anti-tumor Study in Mouse Models

Background: Combination of the prodrug technique with an albumin nanodrug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. Results: : In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the Nab TM technology of paclitaxel palmitate (PTX-PA). Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin NPs (Nab-PTX-PA) remained in the tumor for a longer time post injection. Compared with saline and Abraxane® (nanoparticle albumin-bound (nab)-paclitaxel), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organsand more importantly it inhibited tumor cell proliferation more effectively as compared with commercial Abraxane®. Conclusions: : This carrier strategy for small molecule drugs is based on naturally evolved interactions between LCFAs(Long Chain Fatty Acids) and HSA(human serum albumin), demonstrated here for PTX. Nab-PTX-PA shows higher maximum tolerated doses and increased efficacy in vivo in breast cancer models, as compared to Abraxane for FDA-approved clinical formulations. This novel injectable Nab-PTX-PA platform has great potential as an effective drug delivery system in the treatment of breast cancer.