Recent trends in stabilizing protein structure upon encapsulation and release from bioerodible polymers

Area of Science:

• Biomaterials Science
• Pharmaceutical Technology
• Protein Chemistry

Background:

• Sustained release of pharmaceutical proteins from biocompatible polymers is vital for disease treatment and prevention.
• Protein manufacturing and release processes can compromise protein structure and integrity.
• Understanding and mitigating these stresses are critical for effective drug delivery.

Purpose of the Study:

• To review novel strategies for stabilizing pharmaceutical proteins during encapsulation and release.
• To compare the efficacy of different encapsulation techniques in preserving protein structure.
• To highlight advancements in protecting protein integrity in sustained-release systems.

Main Methods:

• Review of non-invasive technologies for investigating protein destabilization pathways.
• Analysis of stabilization strategies for the water-in-oil-in-water (w/o/w) double emulsion technique.
• Evaluation of alternative methods: solid-in-oil-in-oil (s/o/o) and solid-in-oil-in-water (s/o/w) encapsulation.

Main Results:

• The w/o/w technique often leads to protein instability, requiring additives or increased thermodynamic stability.
• Alternative s/o/o and s/o/w methods suspend dry protein powders in anhydrous organic solvents.
• Protein structure is stabilized in organic phases by "rigidification," kinetically preventing unfolding.

Conclusions:

• Novel encapsulation strategies, particularly s/o/o and s/o/w, offer superior protein stabilization compared to w/o/w.
• Rigidification of proteins in anhydrous organic solvents effectively preserves native structure.
• These advancements enable more rational design of protein-based sustained-release drug delivery systems.