Continuous flow production of size-controllable niosomes using a thermostatic microreactor

Abstract

The new roles of vesicular systems in advanced biomedical, analytical and food science applications demand novel preparation processes designed to reach the new standards. Particle size and monodispersity have become essential properties to control. In this work, key parameters, involved in a microfluidic reactor with hydrodynamic flow focusing, were investigated in order to quantify their effects on niosomes morphology. Particular attention was given to temperature, which is both a requirement to handle non-ionic surfactants with phase transition temperature above RT, and a tailoring variable for size and monodispersity control. With this aim, niosomes with two different sorbitan esters and cholesterol as stabilizer were formulated. High resolution and conventional 3D-printing technologies were employed for the fabrication of microfluidic reactor and thermostatic systems, since this additive technology has been essential for microfluidics development in terms of cost-effective and rapid prototyping. A customised device to control temperature and facilitate visualization of the process was developed, which can be easily coupled with commercial inverted microscopes. The results demonstrated the capability of microfluidic production of niosomes within the full range of non-ionic surfactants and membrane stabilizers.

Vitamin D3 Loaded Niosomes and Transfersomes Produced by Ethanol Injection Method: Identification of the Critical Preparation Step for Size Control

“…The amount of membrane compounds added to the organic phase was optimized using Span ® 60 and Cho 1:1 as membrane components.This formulation was used since it is one of the most common formulations studied in previous works [ 37 , 38 ]. The studied range was changed from 2.2 to 8.3 (% w / w ).…”

“…Multiple formulations of niosomes and transfersomes, based on previous studies [ 13 , 37 , 38 ], were analyzed with a constant mass concentration in the organic phase(2.2%). Small sizes are more interesting from a food, pharmaceutical, and biomedical point of view, since small vesicles can be easily absorbed by human cells.…”

“…For this purpose, VitD3 was selected. It is known that this compound could yield high encapsulation efficiency in vesicles,due to its lipophilic character [ 38 ]. In this set of experiments, a total weight mass of 2.2% was used for all prepared vesicular systems.…”

Continuous-Flow Production of Liposomes with a Millireactor under Varying Fluidic Conditions

“…To address these challenges, millimeter-scale flow reactors (referred to as “millifluidic reactors” or “millireactors”) have been recently developed and employed to produce both inorganic and organic nanomaterials, at volumetric flow rates up to 18 mL/min [ 23 , 29 , 33 , 35 , 36 , 37 , 38 , 39 ]. Notably, scaling-up in these earlier studies enabled increased particle production capacity, while still retaining the fluidic controllability over particle’s properties.…”

“…Notably, scaling-up in these earlier studies enabled increased particle production capacity, while still retaining the fluidic controllability over particle’s properties. Moreover, given their larger dimensions, devices could be manufactured using cost-effective and user-friendly techniques compared to conventional microfabrication methods [ 29 , 35 , 40 ].…”