Microfluidic Synthesis of PEG- and Folate-Conjugated Liposomes for One-Step Formation of Targeted Stealth Nanocarriers |
| |
Authors: | Renee R Hood Chenren Shao Donna M Omiatek Wyatt N Vreeland Don L DeVoe |
| |
Institution: | 1. Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, 20742, USA 3. Biochemical Sciences Division, National Institute of Standards and Technology, Gaithersburg, Maryland, 20899-6313, USA 2. Department of Mechanical Engineering, University of Maryland, College Park, Maryland, 20742, USA 4. University of Maryland, 3139 Glenn L. Martin Hall, Building 088, College Park, Maryland, 20742, USA
|
| |
Abstract: | Purpose A microfluidic hydrodynamic flow focusing technique enabling the formation of small and nearly monodisperse liposomes is investigated for continuous-flow synthesis of poly(ethylene glycol) (PEG)-modified and PEG-folate-functionalized liposomes for targeted drug delivery. Methods Controlled laminar flow in thermoplastic microfluidic devices facilitated liposome self-assembly from initial lipid compositions including lipid/cholesterol mixtures containing PEG-lipid and folate-PEG-lipid conjugates. Relationships among flow conditions, lipid composition, and liposome size were evaluated; their impact on PEG and folate incorporation were determined through a combination of UV–vis absorbance measurements and characterization of liposome zeta potential. Results PEG and folate were successfully incorporated into microfluidic-synthesized liposomes over the full range of liposome sizes studied. Efficiency of PEG-lipid incorporation was inversely correlated with liposome diameter. Folate-lipid was effectively integrated into liposomes at various flow conditions. Conclusions Liposomes incorporating relatively large PEG-modified and folate-PEG-modified lipids were successfully synthesized using the microfluidic flow focusing platform, providing a simple, low cost, rapid method for preparing functionalized liposomes. Relationships between preparation conditions and PEG or folate-PEG functionalization have been elucidated, providing insight into the process and defining paths for optimization of the microfluidic method toward the formation of functionalized liposomes for pharmaceutical applications. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|