Stable Colloidal Drug Aggregates Catch and Release Active Enzymes

Area of Science:

• Colloid and interface science
• Drug discovery and formulation
• Biophysical chemistry

Background:

• Small molecule aggregates are typically problematic in drug discovery.
• However, their colloidal properties offer potential for creating stable delivery vehicles.
• Exploiting these properties could preserve protein activity.

Purpose of the Study:

• To investigate coaggregation of known colloidal aggregators with bis-azo dyes.
• To assess the stability and properties of the resulting coformulated colloids.
• To determine if these colloids can be used for enzyme stabilization and controlled release.

Main Methods:

• Coformulation of seven small molecules with bis-azo dyes.
• Characterization of colloid size and particle size distribution.
• Assessment of colloid stability in high ionic strength and protein concentration solutions.
• Enzyme adsorption, inhibition, and release studies using beta-lactamase, malate dehydrogenase, and trypsin.

Main Results:

• Coformulation reduced colloid size to <100 nm with improved uniformity.
• New colloid formulations demonstrated enhanced stability, particularly in high ionic strength and protein concentrations.
• Coformulated colloids could adsorb and inhibit enzymes.
• Active enzymes could be recovered from resuspended particles up to 72 hours post-adsorption.

Conclusions:

• Coaggregation of small molecules with bis-azo dyes yields stable colloidal vehicles.
• These stable colloids can effectively sequester, stabilize, and isolate enzymes.
• This approach offers a novel method for enzyme preservation and controlled release in drug discovery.