Characterization and distribution of niosomes containing ursolic acid coated with chitosan layer

Abstract

Background and purpose: Ursolic acid (UA) exhibits anti-hepatocarcinoma and hepatoprotective activities, thus promising as an effective oral cancer therapy. However, its poor solubility and permeability lead to low oral bioavailability. In this study, we evaluated the effect of different ratios of Span ® 60-cholesterol-UA and also chitosan addition on physical characteristics and stability of niosomes to improve oral biodistribution. Experimental approach: UA niosomes (Nio-UA) were composed of Span ® 60-cholesterol-UA at different molar ratios and prepared by using thin layer hydration method, and then chitosan solution was added into the Nio-UA to prepare Nio-CS-UA. Findings/Results: The results showed that increasing the UA amount increased the particle size of Nio-UA. However, the higher the UA amount added to niosomes, the lower the encapsulation efficiency. The highest physical stability was achieved by preparing niosomes at a molar ratio of 3:2:10 for Span ® 60, cholesterol, and UA, respectively, with a zeta-potential value of -41.99 mV. The addition of chitosan increased the particle size from 255 nm to 439 nm, as well as the zeta-potential value which increased from -46 mV to -21 mV. Moreover, Nio-UA-CS had relatively higher drug release in PBS pH 6.8 and 7.4 than Nio-UA. In the in vivo study, the addition of chitosan produced higher intensities of coumarin-6-labeled Nio-UA-CS in the liver than Nio-UA. Conclusion and implications: It can be concluded that the ratio of Span ® 60-cholesterol-UA highly affected niosomes physical properties. Moreover, the addition of chitosan improved the stability and drug release as well as oral biodistribution of Nio-UA.

The effectiveness of ursolic acid niosomes with chitosan coating for prevention of liver damage in mice induced by n-nitrosodiethylamine

“…The increase in particle size of chitosan-coated UA niosomes was due to the fact that chitosan had formed a hydrophilic shell on the niosomal surface through electrostatic interaction 15 , 19 . Although the particle size increased, coating chitosan on UA niosomes can enhance its effectiveness.…”

“…The PDI value of Nio-UA remained approximately 0.3 which indicated a relatively homogeneous size distribution. However, chitosan coating significantly increased the PDI value possibly due to the addition of chitosan forming a polymer layer on the surface of the random vesicles 19 , 21 . Zeta potential is a detection index of electric charge on the particle surface.…”

“…Preparation of niosomes was conducted using a thin layer hydration method with a formula composition referred to previous studies as shown in Table 3 17 . UA (sigma-Aldrich, Tokyo, Japan) solution in methanol, span 60 (Wako Pure Chemical Industries, Ltd., Osaka, Japan), and cholesterol (Wako Pure Chemical Industries, Ltd., Osaka, Japan) in chloroform (Merck, Darmstadt, Germany) were mixed in a round bottom flask.…”

“…The organic solvents were then heated in a rotary vacuum evaporator at a temperature of 60 °C until they had all evaporated and a thin lipid layer was formed. This layer was hydrated using 2 ml PBS solution pH 7.4 at 60 °C for 1 h 17 . Sonication was carried out with a water bath sonicator to form niosomes in order to reduce the size of the vesicles.…”

“…In our previous study, optimization of the UA niosome formula found the optimum physical stability in the span 60-cholesterol-UA formula with a mol percent ratio of 3:2:10 17 . Characterization of UA reported that the presence of chitosan showed an increase in the physical stability of UA niosomes.…”