A practical method to trace intracellular and transcellular transport pathways of gold nanoparticles via oral administration

Oral nanoparticles play an important role in improving the bioavailability of poorly water-soluble drug. It is necessary to investigate the interaction of nanoparticles with intestinal epithelial cells. In general, nano-carriers labeled with fluorescent probes are always chosen. However, fluorescent dye via physical loading may leak in complex biological environment and lose its function to trace the transport behavior ofnanoparticles. Fluorescent probes chemically coupled on the nanoparticles may alter the properties of nanoparticles. Therefore, a facile and exact detection method is required to trace intracellular and transcellular pathways of oral nano-medicines. In our study, gold nanoparticles were selected as nano-carriers owing to their unique characteristics of light scattering. The feasibility of gold nanoparticle detection through reflected light signal was tested in different situations, including gold nanoparticle solution, cell and animal level As a result, high resolution image of gold nanoparticles could be detected through reflection mode by confocal laser scanning microscope （CLSM） when excited at a wavelength of 633 nm. The reflected light signal of gold nanoparticles could be clearly shown in different intestinal epithelial cells no matter when they were in fixed or in living state, and the intracellular trafficking and distribution of gold nanoparticles were clearly shown in three-dimensional image. Meanwhile, this method was also applied to rat small intestine in vivo. In conclusion, we believed that this technique was a convenient and precise way to explore the transport behavior of gold nanoparticles via oral administration without fluorescent dye.

Fabrication of deoxycholic acid-modified polymeric micelles and their transmembrane transport

Oral administration is the best way for the most patients due to the good compliance,and intestinal epithelium is the main barrier of oral drug absorption.In order to overcome the small intestine epithelial barrier to orally deliver water-insoluble drugs,deoxycholic acid(DA),a substrate of the intestinal bile acid transporters,conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)(DA-PEOz-PLA)was designed and synthesized,and deoxycholic acid-modified polymeric micelles composed of DA-PEOz-PLA and mPEG-PLA were fabricated to encapsulate model drug coumarin 6(C6)based on intestinal bile acid pathway.The structure of DA-PEOz-PLA was confirmed using 1 H NMR and TLC,and the molecular weight measured by GPC was 10034 g/mol with a PDI of 1.51.The C6-loaded polymeric micelles with drug loading content of 0.085%were characterized to have 40.11 nm in diameter and uniform spherical morphology observed by TEM.Furthermore,the deoxycholic acid-modified polymeric micelles were demonstrated to further enhance the transmembrane transport efficiency.The mechanic study evidenced that anchorage of deoxycholic acid onto the micelles surface enriched their transcellular transport pathway.Therefore,the designed deoxycholic acid-modified polymeric micelles might have a promising potential for oral delivery of water-insoluble drugs.