Antibody buffering of systemically administered lysozyme

Area of Science:

• Pharmacology
• Immunology
• Biochemistry

Background:

• Lysozyme is a therapeutic enzyme.
• Stabilizing plasma pharmacokinetics of therapeutic enzymes is crucial for efficacy.
• Antibody-based strategies offer potential for drug delivery enhancement.

Purpose of the Study:

• To evaluate the pharmacokinetic stabilizing effect of an anti-lysozyme antibody on lysozyme plasma levels.
• To investigate the 'buffering' capacity of an antibody against a model enzyme.
• To explore the potential of antibody buffering for therapeutic enzyme delivery.

Main Methods:

• Radiolabeling of hen egg lysozyme with carbon-14.
• Intravenous infusion of lysozyme with or without murine anti-lysozyme antibody D1.3 in rats.
• Varying dosages of lysozyme and antibody, and administration timing.

Main Results:

• Equimolar anti-lysozyme antibody D1.3 more than doubled lysozyme plasma half-life.
• Increased antibody concentrations further prolonged lysozyme half-life.
• The antibody demonstrated in vivo binding to subsequently administered lysozyme, confirming 'drug loading' capacity.

Conclusions:

• Antibody buffering is a viable strategy to stabilize plasma pharmacokinetics of monovalent therapeutic enzymes.
• This approach holds potential for improving the clinical utility of enzyme-based therapies.
• The anti-lysozyme antibody D1.3 effectively acts as a pharmacokinetic buffer for lysozyme.