Inhaled PYY(3-36) dry-powder formulation for appetite suppression

Area of Science:

• Pharmacology
• Drug Delivery Systems
• Metabolic Research

Background:

• Peptide YY3-36 (PYY3-36) is effective for appetite suppression via injection.
• Needle-free delivery methods, such as inhalation, are being explored for therapeutic applications.
• Systemic pharmacokinetics are crucial for comparing different drug delivery methods and selecting appropriate doses.

Purpose of the Study:

• To evaluate the systemic pharmacokinetics of PYY3-36 delivered via inhalation, comparing it to intraperitoneal (IP) and subcutaneous routes.
• To utilize pharmacokinetic data to select doses for evaluating PYY3-36's efficacy in appetite suppression.
• To assess the potential of inhaled PYY3-36 as a non-invasive therapeutic for appetite control.

Main Methods:

• Dry-powder PYY3-36 formulations were created using spray drying.
• Nose-only inhalation delivery was used in mice, with pharmacokinetic analysis of plasma, lung tissue, and bronchoalveolar lavage fluid.
• Pharmacokinetic data informed the selection of PYY3-36:Dextran T10 doses for appetite suppression studies in mice.

Main Results:

• Inhalation delivery resulted in plasma exposure comparable to IP and subcutaneous routes, even at a 2x higher dose.
• Inhalation doses of 0.22 and 0.65 mg/kg were used for efficacy studies.
• A dose-dependent decrease in food consumption over 4 hours was observed, similar to injectable routes.

Conclusions:

• Pharmacokinetic data effectively guided the selection of doses for pharmacodynamic studies of inhaled PYY3-36.
• Engineered PYY3-36:Dextran T10 particles delivered via the respiratory tract show promise as a non-invasive treatment for appetite suppression.
• Inhalation offers a viable needle-free alternative for PYY3-36 delivery, supporting its potential as a therapeutic agent.