Industrial-scale methods for the manufacture of liposomes and nanoliposomes: pharmaceutical, cosmetic, and nutraceutical aspects

Document Type : Narrative Review


1 Department of Biological Science, Faculty of Science, University of Kurdistan, Sanandaj, Kurdistan, Iran Nanobiotechnology Department, Faculty of Innovative Science and Technology, Razi University, Kermanshah, Iran

2 Australasian Nanoscience and Nanotechnology Initiative (ANNI), 8054 Monash University LPO, Clayton, Victoria 3168, Australia

3 Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa Wellman Centre for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA Department of Dermatology, Harvard

4 Department of Pharmaceutics, School of Pharmacy, Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences

5 Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran


Liposomes are microscale lipid bilayer vesicles, widely employed for solubilizing drugs and delivering them to the body with precise targeting and controlled release. The nanoscale version of liposomes is known as nanoliposome. These biocompatible and biodegradable drug delivery systems have several advantages, such as the ability to be loaded with various drug molecules in physiological conditions. Compared with other delivery systems, such as micelles, polymeric, metallic nanocarriers, or niosomes, liposomes are the most well-established and commercially available carrier, used not only in pharmaceuticals, but also in cosmeceutical and nutraceutical products. However, scaling-up their manufacture and ensuring sufficient stability are significant challenges for liposomes. In this review, we discuss several industrial-scale methods for liposome preparation including organic solvent methods, freeze-drying of double emulsions, heating method, Mozafari method, membrane contactor method, liposome formation by curvature tuning, biomimetic liposomal self-assembly, sonication method, extrusion method, spray drying method, and microfluidic systems. Some factors leading to physicochemical or biological instability and the ways to overcome these challenges are discussed. International agencies'' quality control procedures and regulatory aspects for liposomal and nanoliposomal drug product development are also addressed.

Graphical Abstract

Industrial-scale methods for the manufacture of liposomes and nanoliposomes: pharmaceutical, cosmetic, and nutraceutical aspects


  • Functionalized liposomes can be employed to increase the bioavailability and biodegradability of bioactive agents in physiological conditions.
  • The choice of preparation method should be determined based on the therapeutic objectives.
  • Aggregation, coalescence, agglomeration, or the precipitation of vesicles during preparation or storage can lead to the degradation of the vesicle structure.
  • Solubility properties, functionalization methods, stability of liposomes in physiological conditions, and storage outside the body are the main factors that govern the choice of preparation method.
  • The stability of liposomes during storage is affected by the spray drying and freeze-drying processes.
  • The primary concern of the microfluidics method is the difficulty in scaling up for the industrial application, owing to the inherent volume limitations of the microfluidic devices.


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