title: Microfluidic synthesis of PEG- and folate-conjugated liposomes for one-step formation of targeted stealth nanocarriers.
abstract: OBJECTIVE
  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.
authors: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland 20742, USA.
authors: Renee R
authors: RR
authors: Hood
authors: Chenren
authors: C
authors: Shao
authors: Donna M
authors: DM
authors: Omiatek
authors: Wyatt N
authors: WN
authors: Vreeland
authors: Don L
authors: DL
authors: DeVoe
mesh_terms: D002784:Cholesterol / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D046210:Microfluidic Analytical Techniques / Q000379:methods; D044085:Microfluidics / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; C552831:poly(ethylene glycol)-folate; D011092:Polyethylene Glycols; D005492:Folic Acid; D002784:Cholesterol
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