Polycationic peptide guided spherical ordered self-assembly of biomacromolecules

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Protein Engineering

Background:

• Effective delivery of therapeutic proteins remains a challenge.
• Current methods often require carriers or new molecular entities.
• Controllable, long-acting protein delivery offers significant clinical benefits.

Purpose of the Study:

• To demonstrate controllable, long-acting delivery of therapeutic proteins.
• To investigate the self-assembly of recombinant human interferon-alpha (rhIFN) with a polycationic peptide.
• To characterize the resulting self-assemblies and evaluate their pharmacokinetic profile.

Main Methods:

• Molecular self-assembly directed by a polycationic peptide.
• Phase diagram construction for optimal self-assembly conditions.
• Physico-chemical characterization (morphology, size, XRD, CD).
• In vitro and in vivo dissolution behavior analysis.
• Pharmacokinetic studies following subcutaneous administration.
• Molecular simulations for binding site and mode analysis.

Main Results:

• Recombinant human interferon-alpha (rhIFN) self-assembled into ordered, spherical, semi-crystalline structures.
• Self-assembly was directed by a short polycationic peptide.
• Phase diagrams identified optimal regions for nucleation and growth.
• Dissolution behavior was tunable by adjusting the molar ratio.
• Subcutaneous administration of self-assemblies resulted in prolonged rhIFN blood levels up to seven days.
• Molecular simulations provided insights into binding interactions.

Conclusions:

• Spherical ordered self-assembly of biomacromolecules is a viable strategy for controllable protein delivery.
• This approach enables long-acting therapeutic protein delivery without additional carriers.
• The method offers a promising alternative for enhancing the clinical utility of protein-based therapeutics.