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Updated: May 30, 2025
Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier
Published on: February 8, 2017
Targeting antibodies dissociate from drug delivery liposomes during blood circulation
Unnur J Björgvinsdóttir1, Jannik B Larsen1, Martin Bak1
1Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark (DTU), Kgs. Lyngby, Denmark.
Abstract:
Despite three decades of intense research, active targeting of liposomes have not been successfully achieved in a clinical setting. A potential explanation is that the clinically used liposomes lose their targeting abilities upon circulation. Here, we investigated if DSPE-PEG anchored antibody-based targeting ligands dissociate from clinically relevant drug delivery liposomes during circulation in mice. We found that during 4 h of circulation, a significant fraction of the liposomes lose all targeting ligands, while the liposomes with some targeting ligands remaining on their surface, show a > 50 % reduction in surface density of ligands. This was detected irrespective of antibody format (IgG, Fab, F(ab')2), ability to interact with Fc receptors or linking chemistry. Dissociation of targeting antibodies did however not take place when incubating liposomes in serum, but required an in vivo setup, demonstrating that in vitro setups are unsuitable for quantifying such liposome disassembly processes. The observation unravels a problem that researchers developing targeted drug delivery vehicles should take into account when designing novel formulations.
Insights
Targeting ligands detach from drug delivery liposomes during circulation in mice, hindering active targeting. This dissociation occurs in vivo, not in vitro, impacting the design of novel drug delivery systems.
Area of Science:
- Nanomedicine
- Drug Delivery
- Biotechnology
Background:
- Active targeting of liposomes is crucial for drug delivery but faces clinical challenges.
- Existing liposomes may lose targeting capabilities during circulation, limiting therapeutic efficacy.
Purpose of the Study:
- To investigate the dissociation of antibody-based targeting ligands from drug delivery liposomes during circulation in mice.
- To determine if in vitro methods accurately reflect in vivo ligand stability.
Main Methods:
- Liposomes with DSPE-PEG anchored antibody ligands were circulated in mice for 4 hours.
- Ligand density on liposome surfaces was quantified post-circulation.
- Comparison of ligand stability in vivo versus in vitro (serum incubation).
Main Results:
- A significant fraction of liposomes lost all targeting ligands within 4 hours of circulation.
- Remaining ligands showed a >50% reduction in surface density, irrespective of antibody format or linking chemistry.
- Ligand dissociation occurred in vivo, but not during in vitro serum incubation.
Conclusions:
- Antibody-based targeting ligands dissociate from liposomes during in vivo circulation.
- In vitro assays are inadequate for assessing liposome targeting ligand stability.
- This finding presents a critical challenge for developing effective targeted drug delivery systems.
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