Sweet corn phytoglycogen dendrimers as a lyoprotectant for dry-state protein storage

Area of Science:

• Biochemistry
• Materials Science
• Drug Delivery

Background:

• Protein biotherapeutics require cold-chain storage for stability.
• Lyophilization offers an alternative to cold-chain storage but necessitates optimized excipients.
• Excipients must provide cryoprotection, lyoprotection, and cake formation for dehydrated proteins.

Purpose of the Study:

• To investigate sweet corn phytoglycogens (PG) as dual-function excipients for protein lyophilization.
• To identify specific PG variants with optimal lyoprotective and cake-forming properties.
• To establish PG dendrimers as a new class of excipients for dry protein formulations.

Main Methods:

• Extraction and characterization of 16 phytoglycogen variants (PG1-16) from maize.
• Assessment of PG colloidal stability, protein contaminant levels, and cytocompatibility.
• Evaluation of PG's ability to maintain protein activity through multiple lyophilization cycles.
• Determination of glass transition temperature (Tg') and cake morphology of protein-PG mixtures.

Main Results:

• Phytoglycogen (PG) dendrimers demonstrated both lyoprotective and cake-forming capabilities.
• Specific PG variants (PG1, 2, 9, 13, 15, 16) maintained protein activity post-lyophilization.
• PG13 emerged as a lead candidate due to narrow dispersity, stability, low contaminants, and cytocompatibility.
• Optimal lyoprotection and cake formation by PG13 were density-dependent, requiring at least 5 mg/mL.

Conclusions:

• Phytoglycogen dendrimers represent a novel class of excipients for protein lyophilization.
• PGs offer a promising alternative to traditional excipients, simplifying protein formulation.
• These findings facilitate the development of stable, room-temperature-storable protein biotherapeutics.