Related Experiment Video
Updated: Aug 15, 2025
Microfluidic Production of Lysolipid-Containing Temperature-Sensitive Liposomes
Published on: March 3, 2020
Microfluidic Post-Insertion Method for the Efficient Preparation of PEGylated Liposomes Using High Functionality and
Yuri Sugimoto1,2, Tadaharu Suga1, Naoya Kato1
1Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Introduction:
Targeted liposomes using ligand peptides have been applied to deliver therapeutic agents to the target sites. The post-insertion method is commonly used because targeted liposomes can be prepared by simple mixing of ligand peptide-lipid and liposomes. A large-scale preparation method is required for the clinical application of ligand-peptide-modified liposomes. Large-scale preparation involves an increase in volume and a change in the preparation conditions. Therefore, the physicochemical properties of liposomes may change owing to large alterations in the preparation conditions. To address this issue, we focused on a microfluidic device and developed a novel ligand peptide modification method, the microfluidic post-insertion method.
Methods:
We used integrin αvβ3-targeted GRGDS (RGD) and cyclic RGDfK (cRGD)-modified high functionality and quality (HFQ) lipids, which we had previously developed. First, the preparation conditions of the total flow rate in the microfluidic device for modifying HFQ lipids to polyethylene glycol (PEG)-modified (PEGylated) liposomes were optimized by evaluating the physicochemical properties of the liposomes. The targeting ability of integrin αvβ3-expressing colon 26 murine colorectal carcinoma cells was evaluated by comparing the cellular association properties of the liposomes prepared by the conventional post-insertion method.
Results:
When the RGD-HFQ lipid was modified into PEGylated liposomes by varying the total flow rate (1, 6, and 12 mL/min) of the microfluidic device, as the total flow rate increased, the polydispersity index also increased, whereas the particle size did not change. Furthermore, the RGD- and cRGD-modified PEGylated liposomes prepared at a total flow rate of 1 mL/min showed high cellular association properties equivalent to those prepared by the conventional post-insertion method.
Conclusion:
Microfluidic post-insertion method of HFQ lipids might be useful for clinical application and large-scale preparation of targeted liposomes.
