Microfluidic Assembly of Liposomes with Tunable Size and Coloading Capabilities

  • Jessica R. Hoffman
  • Ennio TasciottiEmail author
  • Roberto MolinaroEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1792)


Liposomes used for the delivery of pharmaceuticals have difficulties scaling up and reaching clinical translation as they suffer from batch-to-batch variability. Here, we describe a microfluidic approach for creating reproducible, homogenous nanoparticles with tunable characteristics. These nanoparticles of sizes ranging from 30 to 500 nm are rapidly self-assembled by controlling the flow rates of ethanol and aqueous streams. This method of microfluidic assembly allows for the efficient encapsulation of both hydrophobic and hydrophilic drugs in the lipid bilayer and particle core, respectively, either separately or in combination.

Key words

Liposomes Nanomedicine Microfluidics Coloading Reproducibility Scale up 



This work was supported by grants RF-2010-2318372 and RF-2010-2305526 from the Italian Ministry of Health, William Randolph Hearst Foundation, The Regenerative Medicine Program Cullen Trust for Health Care (Project ID: 18130014), Brown Foundation (Project ID:18130011), the Hearst Foundation (Project ID: 18130017), the NIH/NCI and the Office of Research on Women’s Health (Grant # 1R56CA213859), and Cancer Prevention and Research Institute of Texas (Project ID: RP170466) to E.T. The authors acknowledge the George J. and Angelina P. Kostas Charitable Foundation and CARIPARO Foundation Ricerca Pediatrica 2016–2018 Grant.


  1. 1.
    Shi J, Xiao Z, Kamaly N, Farokhzad OC (2011) Self-assembled targeted nanoparticles: evolution of technologies and bench to bedside translation. Acc Chem Res 44(10):1123–1134. CrossRefPubMedGoogle Scholar
  2. 2.
    Belliveau NM et al (2012) Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Mol Ther Nucleic Acids 1:e37. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Valencia PM, Pridgen EM, Rhee M, Langer R, Farokhzad OC, Karnik R (2013) Microfluidic platform for combinatorial synthesis and optimization of targeted nanoparticles for cancer therapy. ACS Nano 7(12):10671–10680. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Gaumet M, Vargas A, Gurny R, Delie F (2008) Nanoparticles for drug delivery: the need for precision in reporting particle size parameters. Eur J Pharm Biopharm 69(1):1–9. CrossRefPubMedGoogle Scholar
  5. 5.
    Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65(1–2):271–284. CrossRefPubMedGoogle Scholar
  6. 6.
    He C, Hu Y, Yin L, Tang C, Yin C (2010) Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 31(13):3657–3666. CrossRefPubMedGoogle Scholar
  7. 7.
    Knop K, Hoogenboom R, Fischer D, Schubert US (2010) Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. ChemInform 42:3. CrossRefGoogle Scholar
  8. 8.
    Walsh C et al (2014) Microfluidic-based manufacture of siRNA-lipid nanoparticles for therapeutic applications. Methods Mol Biol 1141:109–120. CrossRefPubMedGoogle Scholar
  9. 9.
    Zhigaltsev IV et al (2016) Production of limit size nanoliposomal systems with potential utility as ultra-small drug delivery agents. J Liposome Res 26(2):96–102. CrossRefPubMedGoogle Scholar
  10. 10.
    Corbo C, Molinaro R, Parodi A, Toledano-Furman NE, Salvatore F, Tasciotti E (2016) The impact of nanoparticle protein corona on cytotoxicity, immunotoxicity and target drug delivery. Nanomedicine 11(1):81–100. CrossRefPubMedGoogle Scholar
  11. 11.
    Wolfram J et al (2014) The nano-plasma interface: implications of the protein corona. Colloids Surf B: Biointerfaces 124:17–24. CrossRefPubMedGoogle Scholar
  12. 12.
    Filion MC, Phillips NC (1997) Toxicity and immunomodulatory activity of liposomal vectors formulated with cationic lipids toward immune effector cells. Biochim Biophys Acta Biomembr 1329(2):345–356. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of North CarolinaChapel HillUSA
  2. 2.Center of Biomimetic MedicineHouston Methodist Research InstituteHoustonUSA
  3. 3.Houston Methodist Orthopedic and Sports MedicineInstitute for Academic Medicine, Houston Methodist Research InstituteHoustonUSA
  4. 4.Department of Medicine, Cardiovascular MedicineHarvard Medical School Brigham and Women’s HospitalBostonUSA

Personalised recommendations