Naturally sourced amphiphilic peptides as paclitaxel vehicles for breast cancer treatment

Rongli Chen; Ergang Liu; Yuefei Fang; Nan Gao; Meng Zhang; Xiaoru Zhang; Wanying Chen; Chuxin Liang; Yu Zhang; Yongzhuo Huang

doi:10.1016/j.bioadv.2024.213824

Naturally sourced amphiphilic peptides as paclitaxel vehicles for breast cancer treatment

Biomater Adv. 2024 May:159:213824. doi: 10.1016/j.bioadv.2024.213824. Epub 2024 Mar 5.

Authors

Rongli Chen¹, Ergang Liu², Yuefei Fang³, Nan Gao³, Meng Zhang⁴, Xiaoru Zhang⁵, Wanying Chen⁶, Chuxin Liang³, Yu Zhang⁷, Yongzhuo Huang⁸

Affiliations

¹ Shenyang Pharmaceutical University, Shenyang 110016, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China.
² Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China. Electronic address: liuergang@zidd.ac.cn.
³ Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China.
⁴ Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
⁵ Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510450, China.
⁶ Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510450, China.
⁷ Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: pharmzy@163.com.
⁸ Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients, Shanghai 201203, China. Electronic address: yzhuang@simm.ac.cn.

PMID: 38490019
DOI: 10.1016/j.bioadv.2024.213824

Abstract

The marketed paclitaxel (PTX) formulation Taxol relies on the application of Cremophor EL as a solubilizer. The major drawback of Taxol is its hypersensitivity reactions and a pretreatment of anti-allergic drugs is a necessity. Therefore, developing an efficient and safe delivery vehicle is a solution to increase PTX treatment outcomes with minimal adverse effects. In this work, we prepared the amphiphilic peptides (termed AmP) from soybean proteins using a facile two-step method. AmP could efficiently solubilize PTX by self-assembling into mixed micelles with D-α-tocopherol polyethylene glycol succinate (TPGS), a common pharmaceutical expedient (PTX@TPGS-AmP). The intravenously administrated PTX@TPGS-AmP exhibited a slow clearance (0.24 mL·(min·kg)^-1) and an enhanced AUC (41.4 μg.h/mL), manifesting a 3.6-fold increase compared to Taxol. In a murine 4T1 tumor model, PTX@TPGS-AmP displayed a superior antitumor effect over Taxol. Importantly, safety assessment showed a high biocompatibility of AmP and an i.v. dose up to 2500 mg/kg led to no observable abnormalities in the mice. In summary, the AmP presents a new green and easily-prepared amphiphilic biomaterial, with promising potential as a pharmaceutical excipient for drug delivery.

Keywords: Amphiphilic peptide; Breast cancer; Drug delivery; Micelles; Paclitaxel.

MeSH terms

Animals
Cell Line, Tumor
Drug Delivery Systems
Mice
Micelles
Neoplasms*
Paclitaxel* / therapeutic use
Peptides
alpha-Tocopherol

Substances

Paclitaxel
Micelles
alpha-Tocopherol
Peptides