Preparation of size-controlled BSA nanoparticles by intermittent addition of desolvating agent

Abstract

In order to see functionality and toxicity of nanoparticles in various food and drug applications, it is important to establish procedures to prepare nanoparticles of a controlled size. Desolvation, a thermodynamically driven selfassembly process for polymeric materials such as bovine serum albumin (BSA), is a commonly used method to prepare nanoparticles. The polymeric molecules form particles of different sizes depending on the preparation conditions such as protein content, pH, ionic strength, concentration of cross-linking agent, agitation speed, amount of desolvating agent such as ethanol, etc. In general, a desolvating agent, acetone or ethanol, is added dropwise continuously in the aqueous BSA solution until that the solution becomes just turbid to form nano-sized particles. However, in many cases the particle sizes from repeated experiments are fluctuating even if the preparation conditions are the same. As a result, standard deviation of average particle size is relatively large. Herein, we suggest that the intermittent addition of desolvating agent can improve reproducibility of BSA nanoparticle preparation. In addition, BSA nanoparticles of a controlled size can be manufactured with narrow particle size distribution. In our study, ethanol was added intermittently into 1 BSA solution at different pHs under stirring at 700 rpm. Amount of ethanol added, intermittent timeline of ethanol addition, and pH of solution were considered as process parameters to be optimized. Effect of the process parameters on size and optical density of the fabricated nanoparticles were studied. The results indicated that the size control of BSA nanoparticle was achieved by adjusting pH. The standard deviation of average size of BSA nanoparticles at each preparation condition was minimized by adding ethanol intermittently. The intermittent addition in polymeric aqueous solution at different pH can be useful for size control for food or drug applications. © Springer-Verlag 2010.