Rapid on-Chip Assembly of Niosomes: Batch versus Continuous Flow Reactors

Abstract

The large-scale continuous production of niosomes remains challenging. The inherent drawbacks of batch processes such as large particle polydispersity and reduced batch-to-batch reproducibility are here overcome by using commercially available microfluidic reactors. Compared to the traditional batch-based film hydration method, herein, we demonstrate that it is possible to carry out the homogeneous, large-scale (up to 120 mg/min) production of niosomes using two different synthesis techniques (the thin film hydration method and the emulsification technique). Niosomes particle size can be controlled depending on the need by varying the synthesis temperature. The high cytocompatibility of the resulting niosomes was also demonstrated in this work on three different somatic cell lines. For the first time, the structure of the niosome multilamellar shell was also elucidated using high-resolution transmission electron microscopy (HR-STEM) as well as their colloidal stability over time (6 weeks) under different storage conditions. The morphology of cryo-protected or as-made niosomes was also evaluated by HR-STEM after freeze-drying. Finally, the dual ability of those synthetic, nonionic, surfactant-based vesicles to carry both hydrophilic and hydrophobic molecules was also here demonstrated by using laser scanning confocal microscopy.

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

“…Regarding temperature effect some authors reported an increase in particle size as temperature increased [24] which were attributed to the bilayer expansion at higher temperature [43]. In our case, such increase in particle size was not observed.…”

“…By controlling the flow, the extension of mixing and hence the size of liposomes, could also be controlled. However, the production of niosomes through microfluidic routes remains less explored, and limited attention has been paid to using HFF technique [22,23,24].…”

Formulation, characterization and evaluation of morusin loaded niosomes for potentiation of anticancer therapy

“…Studies have proven niosomes to be safe without any cytotoxic effects. 34,64,65 As could be seen from (Fig. 3), the cellular viability was above 80% in all the cell lines even at high concentration of particles (1000 mg ml À1 ).…”

Phospholipid‐Free Small Unilamellar Vesicles for Drug Targeting to Cells in the Liver

“…Surfactants, most often supplemented with cholesterol (Chol), can form bilayer vesicles known as niosomes . Niosomal formulations are capable of encapsulating hydrophilic and hydrophobic drugs in the aqueous core and the lipophilic membrane, respectively . Niosomes have been extensively used in the cosmetic industry and studied for topical drug delivery for decades .…”

“…Novel manufacturing strategies are to be investigated for producing diverse formulations. Recently, microfluidics was utilized to produce conventional niosomes; however, it was not possible to incorporate a Chol content higher than equimolar with this technique either . In this study, we utilized a staggered herringbone micromixer (SHM) to engineer nano‐sized vesicles with a high Chol content (>50 mol%).…”