High-throughput analysis of protein stability in polyanhydride nanoparticles

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Polyanhydrides are surface-eroding biomaterials crucial for vaccine and drug delivery.
• Protecting fragile protein therapeutics and vaccine antigens from degradation, especially at higher temperatures, is essential.
• Existing methods for assessing protein stability during delivery are time-consuming and material-intensive.

Purpose of the Study:

• To develop a high-throughput methodology for assessing protein stability during polyanhydride nanoparticle-based delivery.
• To investigate the impact of polymer chemistry and delivery processes (encapsulation, storage, release) on protein stability.
• To identify polyanhydride formulations that effectively stabilize a model protein, bovine serum albumin.

Main Methods:

• Developed a high-throughput screening approach to evaluate protein stability.
• Investigated the effects of polymer chemistry, encapsulation, storage, and release on bovine serum albumin stability.
• Assessed the influence of microenvironment pH, resulting from polymer degradation, on protein integrity.

Main Results:

• The microenvironment pH generated by acidic polymer degradation products was identified as the primary factor negatively impacting protein stability.
• Specific polyanhydride nanoparticles, formulated with 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane and 1,6-bis(p-carboxyphenoxy)hexane, maintained protein antigenicity and structure for one month across various temperatures.
• The developed combinatorial approach reduced investigation time by 25-fold and material requirements by 10-fold compared to conventional methods.

Conclusions:

• The microenvironment pH is critical for maintaining protein stability in polyanhydride delivery systems.
• Selected polyanhydride nanoparticles demonstrate significant potential for preserving protein structure and function in drug and vaccine delivery applications.
• The high-throughput methodology offers a more efficient and cost-effective means for evaluating protein stabilization in biomaterials.