Modified mixed nanomicelles with collagen peptides enhanced oral absorption of Cucurbitacin B: preparation and evaluation

Lan Tang,Lulu Fu,Zhuanfeng Zhu,Yan Yang,Boxuan Sun,Weiguang Shan,Zhenhai Zhang

doi:10.1080/10717544.2018.1425773

Abstract

Polymer nanoparticles modified with collagen peptides (CPs) are an attractive strategy for the oral delivery of active ingredients from Chinese medicine. Thus, in the present study, collagen cationic CPs were simply separated using ion-exchange resin from bovine CPs, to modify mixed nanomicelles (MMs) on the surface to improve the oral bioavailability of Cucurbitacin B (CuB). The physicochemical property of micelles was characterized, which confirmed the successful modification of the nanomicelles. CPs-modified nanomicelles in vitro were found to significantly increase cellular uptake and transportation. Compared to unmodified micelles, the quantity of CPs-modified micelles internalized by Caco-2 cells were 3.74 times greater and the cumulative transportation flux (AP-BL) was 2.81 times greater. The membrane transportation process of CuB-MMs-CPs was found to be associated with energy consumption and clathrin- and caveolin-mediated endocytosis. In vivo studies performed on rats indicated that in comparison to CuB and CuB-MMs, the relative bioavailability of CuB-MMs-CPs increased by 3.43 times and 2.14 times, respectively. In addition, the tumor inhibition caused by CuB-MMs-CPs was increased significantly. Therefore, the nanomicelles co-modified with isolated CPs could act as attractive carriers for oral delivery of CuB.

Highlights

Application of traditional Chinese medicine in the clinical setting prioritizes the route of oral administration, so the efficacy of the administered drug mainly depends on the absorption of active compositions in the intestinal system
With collagen peptides (CPs) modification, the maximum quantity of Cucurbitacin B (CuB) internalized by Caco-2 cell was 3.74 times higher at 4 h than that of unmodified micelles
The results demonstrated that CuB-mixed nanomicelles (MMs), with or without CP modification were of different particle sizes, and the size of CuB mixed nanomicelles (CuB-MMs)-CPs were considerably larger than that of the CuB-MMs

Summary

Introduction

Application of traditional Chinese medicine in the clinical setting prioritizes the route of oral administration, so the efficacy of the administered drug mainly depends on the absorption of active compositions in the intestinal system. Most of the active ingredients from Chinese medicine usually possess low solubility or low permeability through the intestinal epithelial membrane, and even when associated with efflux pumps, their oral bioavailability is considerably low, which restricts the performance of traditional Chinese medicine in terms of clinical efficacy. Oral delivery of these drugs has remained a great challenge and attracted much attention during recent years (Xie et al, 2011). A considerable amount of research on topics such as liposomes, micelles, and solid lipid nanoparticles have been reported to improve drug solubility (Gao et al, 2012; Tapeinos et al, 2017; Zhang et al, 2017). The CPPs were usually prepared by solid phase peptide synthesis or prokaryotic expression, the method which was considered complex and expensive

Methods

Results

Discussion

Conclusion