Scalable solvent-free production of liposomes

J Pharm Pharmacol. 2020 Oct;72(10):1328-1340. doi: 10.1111/jphp.13329. Epub 2020 Jul 16.


Objectives: A major challenge faced with the manufacture of liposomes is the high volumes of organic solvents used during manufacturing. Therefore, we have implemented an organic solvent-free production method for drug-loaded liposomes and demonstrated its applicability with both aqueous core-loaded and bilayer-loaded drugs.

Methods: Liposomes were produced by high shear mixing dry powder lipids with an aqueous buffer, followed by down-sizing using a Microfluidizer processor. Liposomes were purified via tangential flow filtration and characterised in terms of size, polydispersity index, zeta potential and drug loading.

Key findings: Doxorubicin-loaded PEGylated liposomes can be manufactured using this solvent-free method with particle sizes of 100-110 nm, low polydispersity index (PDI) (<0.2) and high drug loading (97-98%). If required, liposomes can be further down-sized via microfluidic processing without impacting drug loading. Similar results were achieved with non-PEGylated liposomes. With bilayer-loaded amphotericin B liposomes, again liposomes can be prepared within a clinically appropriate size range (100-110 nm in size, low PDI) with high drug loading (98-100%).

Conclusions: We apply a simple and scalable solvent-free method for the production of both aqueous core or bilayer drug-loaded liposomes.

Keywords: drug loading; liposomes; manufacturing; particle size; solvent-free.

MeSH terms

  • Amphotericin B / chemical synthesis
  • Amphotericin B / pharmacokinetics
  • Chemistry, Pharmaceutical / methods*
  • Doxorubicin / chemical synthesis
  • Doxorubicin / pharmacokinetics
  • Liposomes / chemical synthesis*
  • Liposomes / pharmacokinetics
  • Phosphatidylcholines / chemical synthesis*
  • Phosphatidylcholines / pharmacokinetics
  • Solvents*


  • Liposomes
  • Phosphatidylcholines
  • Solvents
  • Amphotericin B
  • Doxorubicin