Complement activation by PEGylated liposomes containing prednisolone

Area of Science:

• Biotechnology
• Immunology
• Materials Science

Background:

• PEGylated liposomes can trigger hypersensitivity reactions (HSRs) due to complement system (C) activation.
• This activation is often linked to the negative charge of the PEG anchor molecule on the liposome surface.

Purpose of the Study:

• To investigate if altering the PEGylation profile of liposomes can significantly reduce complement system activation.
• To achieve complement activation levels comparable to nonreactive liposomal formulations.

Main Methods:

• In vitro assays were used to measure complement activation markers (SC5b-9, C3a, C4d, Bb) in normal human serum.
• Liposomes with varied PEG chain length, surface concentration, anchor molecule, and size were tested, including both empty and prednisolone-loaded formulations.

Main Results:

• Most tested PEGylated liposomes showed minimal or no complement activation.
• One formulation, CHOL-PEG2000, demonstrated significant activation of the alternative pathway, indicated by increased SC5b-9 and Bb levels.
• CHOL-PEG2000 liposomes uniquely induced direct C3 conversion without charge or antibody mediation.

Conclusions:

• Altering PEGylation strategies can effectively minimize complement activation by liposomes, potentially reducing HSRs.
• While CHOL-PEG2000 liposomes show promise for understanding liposomal complement activation, their direct C3 conversion suggests caution for clinical development.
• Further in vivo studies are needed to confirm the safety of liposomes with reduced complement activation potential.