Comparative studies of salinomycin-loaded nanoparticles prepared by nanoprecipitation and single emulsion method.

Qin Wang,Puyuan Wu,Chen Xie,Yang Yang,Wei Ren,Rutain Li,Baorui Liu,Chenchen Yang,Qin Liu,Xiqun Jiang,Lifeng Wang,Lixia Yu,Kai Xin

doi:10.1186/1556-276x-9-351

Abstract

To establish a satisfactory delivery system for the delivery of salinomycin (Sal), a novel, selective cancer stem cell inhibitor with prominent toxicity, gelatinase-responsive core-shell nanoparticles (NPs), were prepared by nanoprecipitation method (NR-NPs) and single emulsion method (SE-NPs). The gelatinase-responsive copolymer was prepared by carboxylation and double amination method. We studied the stability of NPs prepared by nanoprecipitation method with different proportions of F68 in aqueous phase to determine the best proportion used in our study. Then, the NPs were prepared by nanoprecipitation method with the best proportion of F68 and single emulsion method, and their physiochemical traits including morphology, particle size, zeta potential, drug loading content, stability, and in vitro release profiles were studied. The SE-NPs showed significant differences in particle size, drug loading content, stability, and in vitro release profiles compared to NR-NPs. The SE-NPs presented higher drug entrapment efficiency and superior stability than the NR-NPs. The drug release rate of SE-NPs was more sustainable than that of the NR-NPs, and in vivo experiment indicated that NPs could prominently reduce the toxicity of Sal. Our study demonstrates that the SE-NPs could be a satisfactory method for the preparation of gelatinase-responsive NPs for intelligent delivery of Sal.

Highlights

Cancer stem cells (CSCs) represent a small proportion of cancer cells that exist in the cancer cell population, which drives tumor growth and recurrence [1,2]
Synthesis of PEG-peptide conjugates Two-hundred milligrams of methoxy-polyethylene glycolNHS and 26 mg of gelatinase-cleavable peptide (PVGLIG) (HD Biosciences Co., Shanghai, China) were dissolved in 3 mL of dimethyl formamide (DMF) containing 3% triethylamine (Et3N) and stirred for 3 h at room temperature to prepare PEG-peptide conjugates
To determine the optimum method for Sal-loaded NP preparation, we made a comparison between NR-NPs prepared with different proportions of poloxamer 188 (F68)

Summary

Introduction

Cancer stem cells (CSCs) represent a small proportion of cancer cells that exist in the cancer cell population, which drives tumor growth and recurrence [1,2]. Tumor drug-resistant cells induced by traditional chemotherapeutics present cancer stem-like characteristics [7]. Several reports and studies published in the last three decades revealed a considerable toxicity of Sal in different kinds of mammals including humans after accidental oral or inhalative intake [14,15,16,17]. To solve these problems, significant efforts have been done, and the widely used are nanoparticles (NPs) due to their satisfying traits

Objectives

Methods

Results

Conclusion