Assembling Alkaline-Responsive Chitosan@Giant Liposomes through an Ultrasound-Integrated Microfluidic Approach

Abstract

This paper presents the fabrication of an alkaline-responsive drug carrier, chitosan@giant liposome (CS-GL), by using an ultrasound-integrated microfluidic approach. On the microfluidic chip, water/oil/water droplets are first prepared and then move through an area of ultrasonic radiation to improve the regional saturation of organic solvent and accelerate its removal. At the same time, phospholipid molecules in the oil phase of the droplets are efficiently self-assembled into giant liposomes (GLs). Subsequently, microfluidic channels combined with an up–down separated structure can help in the fabrication and purification of the GLs. Due to the electrostatic interaction between the amino group of chitosan and the phosphate group of phospholipids, the GLs and chitosan are assembled into CS-GLs. The change of ζ potential after this operation indicates that chitosan is coated on the surface of GLs. The formed CS-GLs are monodispersed with a 54.1 ± 0.7 μm diameter and high drug encapsulation efficiency (∼96%), and the structural integrity can be kept without leakage of contents for more than a week in an acid medium (pH = 1.2). When this structure is placed in an aqueous solution of pH = 7.8, chitosan precipitates gradually and detaches from the GL, causing its rupture. The drug encapsulated in a single CS-GL can be rapidly released within 4 s, and 99.6% of the CS-GL carriers can complete the release within 10 min.

Development of a Microfluidic Formatted Ultrasound‐Controlled Monodisperse Lipid Vesicles' Hydrogel Dressing Combined with Ultrasound for Transdermal Drug Delivery System

“…Determination of U-CMLVs Entrapment Efficiency (EE): Aqueous solution (20,40,60,80, and 100 μg mL −1 ) of 5-FU were prepared sequentially. The peak area of the absorption spectrum for each concentration of the 5-FU solution was measured using high-performance liquid chromatography (HPLC, Agilent 1260).…”

“…According to the previous study, under high-frequency ultrasound, for our prepared 1.409 ± 0.021 μm size U-CMLVs, the diameter is > 1 μm and different from the surrounding medium, so its motion is dominated by acoustic radiation force (ARF). [60][61][62] We calculated ARF and chose high-frequency ultrasound (5 MHz, 0.4 W cm −2 ) to irradiate the dressing we constructed to move the U-CMLVs in the Y-Z plane. Compared the 2 mm height U-CMLVs' dressings with and without high-frequency ultrasound irradiation, the results showed that the U-CMLVs from top to bottom would move to the bottom of the dressing after 2 min of high-frequency ultrasound irradiation (Figure 3a,b and Videos S1 and S2, Supporting Information).…”