Stabilization of Proteins by Nanoencapsulation in Sugar-Glass for Tissue Engineering and Drug Delivery Applications (original) (raw)

Proteins and other biomolecules sequestered in and delivered from polymeric drug delivery systems (DDS) undergo several process and storage-related stresses throughout the life of the product that can result in significant degradation, loss of bioactivity and raise safety concerns. [1-4] Process-related stresses during manufacturing of drug delivery systems can lead to significant protein degradation. These stresses can include elevated temperatures, exposure to liquid and solid hydrophobic interfaces, and vigorous mechanical agitation. [1, 5, 6] A number of approaches have been developed to ameliorate the impact of individual stresses in emulsion-based methods. These include the use of interface stabilizers, [7, 8] protein crystalization [9] and covalent protein modification. [10] Ideally a single approach would protect against all these stresses, yielding excellent encapsulation efficiency and storage stability, while giving burst-free sustained release for any protein and polymer system of interest. Far from meeting this ideal, many approaches for improving one aspect of performance are neutral or deleterious to others. For example, solid-in-oil-in-water (s-o-w) emulsions [3] expose the protein to less solvent-based stress than do water-in-oil-inwater (w-o-w) methods; however, so -w methods have thus far led to reduced encapsulation efficiency or significant burst release. So -w vehicles incorporate proteins as a solid phase through freeze-drying or related processes, allowing inclusion of buffer salts, sugars, and other stabilizing additives. However, bulk freeze-drying yields relatively large protein