Hoffmeister Ion Series Protected Bee Venom Proteins from Damages Induced by Microencapsulation Process

Abstract

PLGA (poly-lactide-co-glycolide) microspheres have more than 30 years of use in drug delivery, but there are some limitations related to protein stability during the process of microencapsulation. During the W1/O phase (in the W1/O/W2 microencapsulation process), hydrophobic interfaces are expanded where interfacial adsorption occurs followed by protein unfolding and aggregation. These problems have limited their usage as vaccine carriers. The Hoffmeister series ions were added to BV (bee venom) proteins to obtain their stability during microencapsulation. A correlation was established between the salts used in aqueous solutions and changes in BV solubility and conformations. The BV α-helical content was stable without protein aggregation or hydrophobic exposition, and a small change at the S-S dihedral angles. BV aggregation was avoided by 20 % in the presence of 40 mM MgCl2, (chaotropic salt) with preserved biological activity. The aim of this work was achieved, which was to obtain the maximum BV stability and can be considered a biotechnological breakthrough because a simple solution like salt addition avoided heterologous proteins usage to reach protein stability. Keywords: Nanomedicine, venom immunotherapy, protein stability, Protein microencapsulation, vaccine carriers, vaccine adjuvants, Drug Content Assay