Preparation of albumin nanoparticles: Optimum size for cellular uptake of entrapped drug (Curcumin)

Abstract

Several nanosytems have previously been reported to increase the bio-availability of curcumin, however most of these studies were restricted to a particular size of nanosystem. The present study is aimed to understand the size-uptake relationship of curcumin loaded albumin nanoparticles to determine the optimal size for maximum uptake in the target cell. For this, human serum albumin (HSA) nanoparticles in the size range of 25-250 nm were prepared by using dithiothreitol (DTT) and sodium deoxycholate (NaDC) as reducing and stabilizing agents respectively and characterised by dynamic light scattering (DLS), zeta (ζ) –potential and transmission electron microscope (TEM). The interaction of curcumin with HSA nanoparticles was investigated by UV–vis and fluorescence spectroscopy which indicated that loading efficiency and the binding constant of curcumin with HSA nanoparticles increased with increase in particle size. The uptake of curcumin from these nanoparticles was followed in human lung carcinoma (A549) cells. HSA nanoparticles of ∼125 nm facilitated maximum cellular uptake of curcumin suggesting it to be the optimal size for delivering hydrophobic drugs. Compared to free drug, curcumin entrapped in to cross linked HSA nanoparticles showed not only improved cellular uptake but also the increased the cytotoxicity in A549 cells. Notably, HSA nanoparticles prepared by thermal denaturation method (without using DTT) while maintaining uniform size, shape and surface charge exhibited lesser loading efficiency and cellular uptake of curcumin. Taken together, present study demonstrates a modified chemical method of preparing bio-compatible HSA nanoparticles, their potential use as nano-carrier for hydrophobic drug and the optimal size for maximum cellular uptake.