Effect Of Chitosan Micro/Nano Particles On Berberine Absorption In Intestine

Objective: The decoction of Chinese Medicine has the advantages of fast absorption and fast effect. Therapeutic effect of decoction was affected not only by the prescription, but also affected by the solid particles formed during decocting. Chitosan particles(CS-Ps) were prepared by electrostatic spraying technique to simulate the polysaccharide particle system in decoction. The effects of CS-Ps with different size or different zeta potential on berberine absorption in intestine were evaluated.Method: In this study, the chitosan(Mw=13,000-15,000 Da, degree of deacetylation= 95%) was used to prepare the CS-Ps with different particle size by method of high voltage electrostatic spray. The chitosan grafted with polyethylenimine(PEI) was used to prepare the CS-Ps with different Zeta potential. Particle size and zeta potential distribution of CS-Ps were assessed by the laser granularity analyzer. The morphological characteristics were observed by scanning electron microscope(SEM). In this study, the effects of CS-Ps on the intestine absorption and intestinal absorption into plasma of berberine were investigated by single pass intestinal perfusion. In order to investigate the mechanism of CS-Ps on berberine absorption, the existing state of berberine and CS-Ps in the perfusion fluid was analysied by high speed centrifugation. At last, the effect of CS-Ps on the epithelial cell layer of ileum was analysied by fluorescent yellow absorbed by paracellular.Results: CS-Ps made by electrostatic spraying technique has spherical shape, smooth surface and uniform particle size. In the CS-Ps group with different particle size, the zeta potentials were(23.1±4.22),(26.5±4.65),(27.4±5.07) and(25.4±5.12) m V repectively and the particle sizes were(160±20),(325±30),(456±50) and(918±140) nm. In the CS-Ps group with different zeta potentials, the particle sizes were(312±28),(320±30) and(338±37) nm, and the zeta potentials were(6.8±4.27),(16.8±1.5) and(28.6±2.5) m V. The results of single pass intestinal perfusion showed that the CS-Ps group with different particle sizes could impove the intestinal absorbtion with varying degrees. Particle with size around 350 exhibited remarable higher berberine absorption than others. When particle size bigger than 500 nm, CS-Ps had no absorption promoting effect. The absorption promotion effect of CS-Ps was also related to the surface zeta potential. CS-Ps with higher surface potential has significant promotive effect on berberine absorption. In the CS-Ps groups, the berberine absorption into plasma and in Peyer's patches were much higher than those in control groups. We speculated that the absorption of berberine and CS-Ps were not independent with perfusion fluid, but a composite of berberine and CS-Ps. And CS-Ps could open the tight junction of epithelial cell in intesstine.Conclusions: The promotive effect of CS-Ps on berberine absorption had a threshold value related to the particle size and the surface Zeta potential. CS-Ps with higher surface potential has stronger absorption promoting effect. The promotive effect of CS-Ps on berberine absorption in intestine is that berberine can be abosrbed by CS-Ps, which can enter blood circulation by the phagocytosis of M cells. At the same time, CS-Ps can open the tight junctions, and then improve drug absorption.