Juan Du,1,* Li-Li Shi,2,* Wei-Wei Jiang,3 Xue-Ai Liu,3 Xin-Hong Wu,3 Xiang-Xiang Huang,3 Ming-Wei Huo,3 Ling-Zhi Shi,3 Jingjian Dong,2 Xiaohong Jiang,2 Renyu Huang,4 Qing-Ri Cao,3 Wenzhou Zhang1 

1Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China; 2College of Medicine, Jiaxing University, Jiaxing, People’s Republic of China; 3College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, People’s Republic of China; 4College of Social Science, Soochow University, Institute of Culture and Tourism Development, Soochow University, Suzhou, 215123, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Wenzhou Zhang, Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China, Email hnzzzwzx@sina.com Qing-Ri Cao, College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Jiangsu, 215123, People’s Republic of China, Email qrcao@suda.edu.cn

Background: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges.
Methods: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated.
Results: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX.
Conclusion: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations.

Keywords: DTX-BSA nanoparticles, thermal-driven self-assembly, microfluidic technology, in-vitro release, pharmacokinetics