Several natural and synthetic proteins of pharmacological importance (including, but not limited to, lysozyme and insulin) are prone to aggregation into insoluble polymeric fibrils, a biologically and industrially unwanted feature.
Taken together, the data accumulated and knowledge gained will further facilitate nanoparticle design and production with insulin or lysozyme-related protein encapsulation. The results obtained depict the atomistic intra- and intermolecular interaction details of the homo-oligomerization and confirm the propensity to form fibrils. We have employed various biophysical methods such as NMR spectroscopy, X-ray crystallography, Thioflavin T fluorescence, and atomic force microscopy in conjugation with molecular modeling to improve the understanding of interaction dynamics during homo-oligomerization of lysozyme (human and hen egg) and insulin (porcine, human, and glargine). The knowledge of the intra- and intermolecular interaction profiles has cardinal importance for the design of encapsulation protocols. Despite the vivid structural knowledge of lysozyme and insulin, the environment-dependent oligomerization (dimer, trimer, and multimer) and associated structural dynamics remain elusive. Encapsulating lysozyme and insulin in micellar nanoparticles probably would prevent aggregation and facilitate oral drug delivery. Insulin and lysozyme share the common features of being prone to aggregate and having biomedical importance.
0 kommentar(er)
