Stimuli-responsive polypeptide nanogels for trypsin inhibition

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Biochemistry

Background:

• Inflammatory processes involve mediators like trypsin.
• Developing effective delivery systems for therapeutic proteins is crucial.
• α1-antitrypsin (AAT) is a natural serine protease inhibitor with therapeutic potential.

Purpose of the Study:

• To develop novel polypeptide nanogel depots for the delivery of α1-antitrypsin (AAT).
• To investigate the loading capacity, release profiles, and inhibitory efficiency of AAT-loaded nanogels.
• To evaluate the potential of these nanogels in inhibiting the inflammatory mediator trypsin.

Main Methods:

• Synthesis of two types of polypeptide nanogels: PHEG-Tyr and Nα-Lys-NG.
• Preparation of nanogels via HRP/H2O2-mediated crosslinking in inverse miniemulsions.
• Characterization of nanogel properties using dynamic light scattering and zeta potential measurements.
• Optimization of loading capacity and release profiles using bovine serum albumin, followed by AAT loading.
• In vitro inhibition studies to assess the enzymatic activity of trypsin.

Main Results:

• Both PHEG-Tyr and Nα-Lys-NG nanogels demonstrated pH and temperature-stimuli responsive behavior.
• Nα-Lys-NG nanogels achieved a maximum AAT loading capacity of 20%.
• A burst release of AAT was observed within the first 6 hours, facilitating rapid trypsin inhibition.
• AAT-loaded nanogels exhibited higher inhibitory efficiency against trypsin compared to free AAT.
• Non-loaded nanogels also showed trypsin inhibitory activity due to their amino acid composition.

Conclusions:

• Hydrophilic, biocompatible, and biodegradable polypeptide nanogels are effective depots for AAT delivery.
• These nanogels enhance the inhibitory efficiency of AAT against trypsin.
• The inherent properties of the nanogels contribute to their therapeutic potential in managing trypsin-mediated inflammation.