Amorphous Nanosuspensions Aggregated from Paclitaxel⁻Hemoglobulin Complexes with Enhanced Cytotoxicity

Chao Qin; Xiaofei Xin; Xue Pei; Lifang Yin; Wei He

doi:10.3390/pharmaceutics10030092

Amorphous Nanosuspensions Aggregated from Paclitaxel⁻Hemoglobulin Complexes with Enhanced Cytotoxicity

Pharmaceutics. 2018 Jul 13;10(3):92. doi: 10.3390/pharmaceutics10030092.

Authors

Chao Qin¹, Xiaofei Xin², Xue Pei³, Lifang Yin⁴, Wei He⁵

Affiliations

¹ Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. 1020142415@cpu.edu.cn.
² Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. 15311010037@stu.cpu.edu.cn.
³ Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. xuepeicpu@gmail.com.
⁴ Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. 1019940752@cpu.edu.cn.
⁵ Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. weihe@cpu.edu.cn.

Abstract

Amorphous nanosuspensions (ANSs) enable rapid release and improved delivery of a poorly water-soluble drug; however, their preparation is challenging. Here, using hemoglobin (Hb) as a carrier, ANSs aggregated from paclitaxel (PTX)⁻Hb complexes were prepared to improve delivery of the hydrophobic anti-cancer agent. An affinity study demonstrated strong interaction between Hb and PTX. Importantly, the complexes could aggregate into <300 nm ANSs with high drug loading, which acidic condition facilitated their formation. Furthermore, the ANSs possessed improved cytotoxicity against cancer cells over the crystalline nanosuspensions. Taken together, ANSs aggregated from PTX⁻Hb complexes were developed, which could kill cancer cells with high efficiency.

Keywords: affinity; amorphous; cytotoxicity; drug-protein complexes; nanosuspensions.