A superposable double-gradient droplet array chip for preparation of PEGDA microspheres containing concentration-gradient drugs

Abstract

This article describes a superposable double-concentration-gradient droplet array chip, which allows a variety of concentration combinations of two components to be formed simultaneously. The concentration gradients generated from two layers of the chip could be arbitrarily superimposed by adjusting the center angle between the two bonding layers. With the aqueous phase flow rate of 1.0 μL min−1 and the oil phase flow rate of 30.0 μL min−1, the droplets about 58 μm in diameter were produced, and the coefficients of variation were below 6.0% for single channel and 5.7% for all the channels. Using a dual-32-channel superposable gradient droplet array chip, poly(ethylene glycol) diacrylate (PEGDA) microspheres containing concentration-gradient combinations of rhodamine B and fluorescein were fabricated to demonstrate the capability of PEGDA for encapsulating hydrophilic and hydrophobic substances, as well as the proper concentration-gradient distribution. Furthermore, PEGDA microspheres loaded with two anticancer drugs, hydrophilic doxorubicin hydrochloride and hydrophobic paclitaxel, of 17 concentration combinations were simultaneously prepared. The drug-induced apoptosis of human uterine cervix cancer cells was investigated using the dual-drug-loaded PEGDA microspheres. The optimum synergistic concentration combination of the two drugs was 12.5 μg mL−1 for doxorubicin hydrochloride and 43.75 μg mL−1 for paclitaxel according to the preliminary screening. The superposable double-gradient droplet array generator was demonstrated to be a promising platform for screening multiple drug combination in microcarriers.