Liposomes as sustained release system for human interferon-gamma: biopharmaceutical aspects

Area of Science:

• Biopharmaceutical Sciences
• Immunology
• Materials Science

Background:

• Interferon-gamma (IFNgamma) is a promising vaccine adjuvant but suffers from rapid degradation.
• Liposomal formulations offer potential for sustained release but require optimization.
• No prior studies have focused on optimizing liposomal IFNgamma characteristics for therapeutic use.

Purpose of the Study:

• To develop and characterize liposomal formulations of recombinant human IFNgamma (hIFNgamma).
• To evaluate the in vitro and in vivo performance of these liposomal formulations.
• To optimize liposome composition for enhanced stability and controlled release of hIFNgamma.

Main Methods:

• Preparation of various liposomal formulations of hIFNgamma using the film hydration method.
• In vitro characterization including association efficiency and bioactivity assays.
• In vivo studies in mice to assess cytokine release kinetics and residence time after subcutaneous administration.

Main Results:

• High association efficiency (>80%) and preserved bioactivity of hIFNgamma in large, multilamellar liposomes.
• Inclusion of negatively charged phospholipids is critical for high association efficiency via electrostatic interactions.
• Liposomal encapsulation prolonged hIFNgamma residence time at the injection site up to 7 days, a 4-fold increase in AUC.
• Increased liposome bilayer rigidity significantly reduced burst release and extended residence time 19-fold compared to free cytokine.

Conclusions:

• Liposomal formulation is a viable strategy to overcome IFNgamma's rapid biodegradation and clearance.
• Liposome composition, particularly lipid charge and bilayer rigidity, critically influences protein association, release kinetics, and in vivo residence time.
• These findings provide a basis for rational design of liposomal IFNgamma adjuvants for enhanced vaccine efficacy against cancer and infectious diseases.