Construction and cellular uptake evaluation of redox-responsive docetaxel prodrug self-assembled nanoparticles

Abstract

Docetaxel (DTX) solution has some serious adverse side effects. A redox-responsive DTX prodrug synthesized in our laboratory was used to prepare DTX prodrug self-assembled nanoparticles (DSNPs) with the method of nanoprecipitation. This study aimed at optimizing the formulation to develop stable preparation for the delivery of DTX. Single-factor test was used to evaluate the effects of the preparation concentration of DTX prodrug, stirring speed, the types of stabilizers and temperature on the prescription process of DSNPs. The particle size and polydispersity index were selected as the evaluation indexes. The entrapment efficiency, drug-loading, size distribution and zeta potential were characterized by UPLC and Zetasizer, respectively. The stability and cellular behavior of DSNPs were investigated by Zetasizer, LC-MS/MS and confocal laser scanning microscope, respectively. The particle size, entrapment efficiency and drug-loading of DSNPs were 173.8 ± 1.4 nm, 98.8% ± 0.1%, and 47.8% ± 0.9%, respectively. DSNPs showed good stability during the storage of 30 days, and were taken into the cells in a time-dependent and concentration-dependent manner. The method of nanoprecipitation could be used to entrap DTX. The preparation method was simple, and the quality of DSNPs was stable and reliable. Through the optimization of the formulation, we obtained uniform and stable DSNPs, which could escape from lysosomes of tumor cells. The optimized formulations were stable for intravenous administration. This study could provide scientific support for the development of nano-drug delivery system of small anti-tumor drug.

Advances in redox-responsive drug delivery systems of tumor microenvironment

“…Disulfide bonds can also link two moieties together even they are with different roles (Fig. 1 d) [ 47 ], which is a good strategy to make the structure and function of carriers more abundant [ 48 ]. Linking two polymers which are hydrophilic and hydrophobic respectively via disulfide bonds can form an amphiphilic copolymer and then self-assemble into micelles [ 49 – 52 ], which can deliver hydrophobic drugs and improve their solubility.…”

Probing the Superiority of Diselenium Bond on Docetaxel Dimeric Prodrug Nanoassemblies: Small Roles Taking Big Responsibilities

“…The Taxotere concentrate injection and the final dilution must be used within 6 h due to stability considerations. [ 4 ] These problems severely limit the clinical application of Taxotere. Rational design of high‐efficient drug delivery systems with low toxicity is crucial for chemotherapy.…”

In vitro anticancer activity of folate-modified docetaxel-loaded PLGA nanoparticles against drug-sensitive and multidrug-resistant cancer cells

“…Only thereafter, the cell death occurs by both apoptotic and non-apoptotic pathways. It is logical to assume [and this assumption is confirmed by the experimental results reported (Adesina et al 2014;Manoochehri et al 2013;Patel et al 2018;Pradhan et al 2013;Ren et al 2018), etc.] that the cytotoxic effect of docetaxel-loaded nanoparticles should manifest later than that of free docetaxel.…”