The albumin-based nanoparticle formation in relation to protein aggregation

Abstract

Albumin is an attractive protein for the preparation of nanoparticle with possible therapeutic applications, due to its biodegradable, nontoxic, non-immunogenic, and metabolizable properties. Many studies have investigated the formation of albumin nanoparticles, generally by the desolvation or coacervation approaches. One of the most important parameters that should be considered in the formation of nanoparticles is their morphology (size and shape). There are many proposals to control the nanoparticle size, but it remains a challenge for researchers yet. In this study, we showed that control of BSA-based nanoparticles/microparticles size could be achieved by varying the temperature and pH and therefore controlling the rate of aggregation. The aggregation behavior was monitored by UV-Vis spectroscopy, SEM, and dye-binding assay. Our results provide more options for the size and shape control of BSA-based nanoparticle in natural buffer systems. The aggregation of BSA at different temperatures within the range of 50-80 °C were studied under the effect of different pHs in the range of 4.7-6.2. In this research, we found that protein aggregation under extreme conditions of pH and temperature, or at the pH near to pI appears to be amorphous, and at the pH above the pI seems to be the amyloid fibril structure. In some instances where the aggregation is neither too fast nor too slow, in the initial phase of the aggregation process, nanoparticle structures can be identified and separated by mechanistic approaches. This observation suggests that the best condition for monitoring the formation of albumin-based nanoparticles could be pH 5.7, 70 °C. Satisfactory rationalization of all aspects of our experimental observation requires further and more detailed study.

Keywords: Amorphous aggregation; Amyloid aggregation; BSA; Nanoparticle.