Precise control of liposome size using characteristic time depends on solvent type and membrane properties

Abstract

Controlling the sizes of liposomes is critical in drug delivery systems because it directly influences their cellular uptake, transportation, and accumulation behavior. Although hydrodynamic focusing has frequently been employed when synthesizing nano-sized liposomes, little is known regarding how flow characteristics determine liposome formation. Here, various sizes of homogeneous liposomes (50–400 nm) were prepared according to flow rate ratios in two solvents, ethanol, and isopropyl alcohol (IPA). Relatively small liposomes formed in ethanol due to its low viscosity and high diffusivity, whereas larger, more poly-dispersed liposomes formed when using IPA as a solvent. This difference was investigated via numerical simulations using the characteristic time factor to predict the liposome size; this approach was also used to examine the flow characteristics inside the microfluidic channel. In case of the liposomes, the membrane rigidity also has a critical role in determining their size. The addition of cholesterol enhanced membrane properties such that the liposome size increased (40–530 nm). However, the interposition of short-chain lipids de-aligned the bilayer membrane, leading to its degradation; this decreased the liposome size. Adding short-chain lipids linearly decreased the liposome size (130–230 nm), but at a shallower gradient than that of cholesterol. This analytical study expands the understanding of microfluidic environment in the liposome synthesis by offering design parameters and their relation to the size of liposomes.

Preparation of lipid nanoparticles by micro-mixer Process simulation and experimental study

“…From Figure 8, it is evident that the optimized structure can mix the liquids in the channel more quickly. This faster mixing is more conducive to the preparation of smaller-sized lipid nanoparticles, providing a larger operating space for the subsequent delivery of drugs by the lipid nanoparticles [13].…”

The application strategy of liposomes in organ targeting therapy

“…Different types of liposomes exhibit different functions in terms of drug loading and delivery. Smaller liposomes, for instance, possess enhanced ability of various bodily barriers penetration, thereby facilitating passive targeted drug delivery (Choi et al, 2023; Dimov et al, 2017). Conversely, larger liposomes improve drug encapsulation efficiency and offer promising potential for surface modifications, thereby evaluating drug enrichment (Bian et al, 2022; Khan et al, 2020).…”

Microfluidic production, stability and loading of synthetic giant unilamellar vesicles

“…Compared to the conventional techniques, microfluidic approaches for producing liposomes exhibit some significant advantages, such as control over the vesicle size, improved cargo encapsulation efficiency, and higher reproducibility 11,12 . For example, microfluidic chips using hydrodynamic focusing allow for the production of liposomes with fine-tuned sizes, and chips using a double-emulsion-droplet-based approach provide excellent encapsulation efficiencies into larger vesicles [13][14][15] .…”