Encapsulation of active pharmaceutical ingredients into liposomes via centrifugation of w/o nano-emulsions

Prof. Dr. H. Nirschl1), Karlsruhe Institute of Technology (KIT)/Germany

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Prof. Dr. Hermann NIrschlProcess Machines, Institute of Mechanical Process Engineering and Mechanics, Karlsruhe Institute of Technology, Karlsruhe/Germany

People involved

Kirsten Ullmann (PhD fellow sponsored by the PRC) - KIT, Germany (kirsten.ullmann@kit.edu)

Dr. Gero Leneweit - Carl Gustav Carus-Institute, Germany


While the previous project [Production of liposomes by centrifugation of water in oil emulsions] addressed the characterization of the applied substances to produce liposomes from a water-in-oil (w/o) nano-emulsion, primary tensiometry and nano-emulsions,1)2)3)4)5)6) this research project focuses on the optimization of liposome production process.

The proof of concept of the flotation of aqueous droplets from a w/o nano-emulsion to an aqueous phase by centrifugation shows advantages in comparison to known liposome production methods: the use of solvents is redundant, and the encapsulation efficiency of hydrophilic model substances is higher than anything described in literature so far, with the potential to approach complete encapsulation. The feasibility of encapsulating several model substances will be investigated and the production process by addressing the influence of phospholipids and the utilized hydrophobic phase on the encapsulation efficiency will be evaluated. Additionally, the determination of the liposome size and stability after centrifugation and release of encapsulated substance is investigated including the influence of an isotonic buffer on the stability. As the development is driven by engineering aspects, process parameters such as the influence of temperature and centrifugal force are examined. The key elements of this study bear a strong potential for large scale industrial applications.

Benefit for the community

The following benefits are expected for researchers in the field of phospholipid science, industry and society:

  • Determination and quantification of successful encapsulation of macromolecular model API, especially proteins and RNA, by establishing a method based on spectroscopy.
  • Based on specific characteristics of the encapsulated substances, API and PL, recommendations about the possible interactions and required process parameters for optimized liposome production are given.
  • Industrial application for a liposomal encapsulation with a successful method that is controllable.
  • Novel drug delivery systems can open completely new application routes for emerging API classes such as RNA and proteins, offering chances for novel treatments of life-threatening diseases.

Visit the supervisors lab


Hildebrandt E, Sommerling JH, Guthausen G, Zick K, Stürmer J, Nirschl H, Leneweit G, 2016
Phospholipid adsorption at oil in water versus water in oil interfaces. Implications for interfacial densities and bulk solubilities
Colloid Surf. A 505, 56–63
Hildebrandt E, Dessy A, Sommerling JH, Guthausen G, Nirschl H, Leneweit G, 2016
Interactions between Phospholipids and Organic Phases – Insights in Lipoproteins and Nanoemulsions
Langmuir 32, 5821–5829
Sommerling JH, Uhlenbruck N, Leneweit G, Nirschl H, 2017
Transfer of colloidal particles between two non-miscible liquid phases
Colloid Surf. A 535, 257–264
Sommerling JH, de Matos MBC, Hildebrandt E, Dessy A, Kok RJ, Nirschl H, Leneweit G, 2018
Instability Mechanisms of Water-in-Oil Nanoemulsions with Phospholipids: Temporal and Morphological Structures
Langmuir 34, 572–584
Hildebrandt E, Nirschl H, Kok RJ, Leneweit G, 2018
Adsorption of phospholipids at oil/water interfaces during emulsification is controlled by stress relaxation and diffusion
Soft Matter 14, 3730–3737
de Matos MBC, Miranda BS, Rizky Nuari Y, Storm G, Leneweit G, Schiffelers RM, Kok RJ, 2019
Liposomes with asymmetric bilayers produced from inverse emulsions for nucleic acid delivery
J. Drug Target. 27, 681-689
Publications derived from the project:
Ullmann K, Poggemann L, Nirschl H, Leneweit G, 2020
Adsorption Process for Phospholipids of Different Chain Lengths at a Fluorocarbon/Water Interface studied by Du Noüy Ring and Spinning Drop
Colloid and Polymer Science 298, 407-417
Ullmann K, Leneweit G, Nirschl H, 2021
How to Achieve High Encapsulation Efficiencies for Macromolecular and Sensitive APIs in Liposomes
Pharmaceutics 13, 691
Ullmann K, Fachet L, Nirschl H, Leneweit G, 2023
Monolayer/Bilayer Equilibrium of Phospholipids in Gel or Liquid States: Interfacial Adsorption via Monomer or Liposome Diffusion?
Gels 9, 803
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