Evaluation of the PEG Density in the PEGylated Chitosan Nanoparticles as a Drug Carrier for Curcumin and Mitoxantrone

Yao Chen; Di Wu; Wu Zhong; Shuwen Kuang; Qian Luo; Liujiang Song; Lihua He; Xing Feng; Xiaojun Tao

doi:10.3390/nano8070486

Evaluation of the PEG Density in the PEGylated Chitosan Nanoparticles as a Drug Carrier for Curcumin and Mitoxantrone

Nanomaterials (Basel). 2018 Jul 1;8(7):486. doi: 10.3390/nano8070486.

Authors

Yao Chen¹, Di Wu², Wu Zhong³, Shuwen Kuang⁴, Qian Luo⁵, Liujiang Song⁶, Lihua He⁷, Xing Feng⁸, Xiaojun Tao⁹

Affiliations

¹ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410013, China. ychen@smail.hunnu.edu.cn.
² Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410013, China. iswudi@smail.hunnu.edu.cn.
³ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410013, China. zwu123@smail.hunnu.edu.cn.
⁴ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410013, China. shwkuang@smail.hunnu.edu.cn.
⁵ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410013, China. luoqian1996@smail.hunnu.edu.cn.
⁶ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410013, China. song1221@hunnu.edu.cn.
⁷ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410013, China. hlh197@hunnu.edu.cn.
⁸ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410013, China. fengxing@hunnu.edu.cn.
⁹ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410013, China. xjtao@hunnu.edu.cn.

Abstract

Polyethylene glycolated (PEGylated)curcumin-grafted-chitosan (PCC) conjugates were synthesized with three PEG/chitosan feed molar ratios (1/5, 1/7.5, and 1/10), namely PCC1, PCC2 and PCC3. Chemical structures of these conjugates were characterized by Fourier transform infrared (FTIR) and proton nuclear magnetic resonance (¹H NMR). The degrees of substitution (DS) of PEG were 0.75%, 0.45% and 0.33%, respectively, for PCC1, PCC2 and PCC3by ¹H NMR analysis. Self-assembled PCC nanoparticles (NPs) were spherical as observed in transmission electron microscope images. Mitoxantrone (MTO)-loaded PCC NPs were prepared to analyze the particle size, zeta potential, drug loading, drug release and in vitro cytotoxicity. The MTO-loaded PCC3 NP (DS = 0.33%) possessed the smallest size (~183.1 nm), highest zeta potential (~+34.0 mV) and the largest loading capacity of curcumin (CUR, ~16.1%) and MTO (~8.30%). The release results showed that MTO-loaded PCC3 NP demonstrated the lowest percentage of MTO release and increased as pH decreased, but the CUR release could only be detected at pH 4.0. In the cytotoxicity study, MTO-loaded PCC3 NP displayed the highest cytotoxicity in HepG2 cell line and the best synergistic effect among the tested NPs. Our results suggest that the DS of PEG has impacts on the structures and functions of PCC NPs: the smaller DS of PEG was associated with the smaller size, the higher zeta potential, the slower drug release, and the higher cytotoxicity of NPs.

Keywords: PEG; chitosan nanoparticles; curcumin; mitoxantrone; synergism.