Recent trends in stabilizing protein structure upon encapsulation and release from bioerodible polymers.
Sustained release of pharmaceutical proteins from biocompatible polymers offers new opportunities in the treatment and prevention of disease. The manufacturing of such sustained-release dosage forms, and also the release from them, can impose substantial stresses on the chemical integrity and native, three-dimensional structure of proteins. Recently, novel strategies have been developed towards elucidation and amelioration of these stresses. Non-invasive technologies have been implemented to investigate the complex destabilization pathways that can occur. Such insights allow for rational approaches to protect proteins upon encapsulation and release from bioerodible systems. Stabilization of proteins when utilizing the most commonly employed procedure, the water-in-oil-in-water (w/o/w) double emulsion technique, requires approaches that are based mainly on either increasing the thermodynamic stability of the protein or preventing contact of the protein with the destabilizing agent (e.g. the water/oil interface) by use of various additives. However, protein stability is still often problematic when using the w/o/w technique, and thus alternative methods have become increasingly popular. These methods, such as the solid-in-oil-in-oil (s/o/o) and solid-in-oil-in-water (s/o/w) techniques, are based on the suspension of dry protein powders in an anhydrous organic solvent. It has become apparent that protein structure in the organic phase is stabilized because the protein is "rigidified" and therefore unfolding and large protein structural perturbations are kinetically prohibited. This review focuses on strategies leading to the stabilization of protein structure when employing these different encapsulation procedures.
Pérez
Caroline
C
University of Puerto Rico, Department of Chemistry, San Juan 00931-3346, USA.
Castellanos
Ingrid J
IJ
Costantino
Henry R
HR
Al-Azzam
Wasfi
W
Griebenow
Kai
K
D001672:Biocompatible Materials; D002626:Chemistry, Pharmaceutical / Q000639:trends; D003692:Delayed-Action Preparations; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D011108:Polymers; D011506:Proteins