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.

Objectives For designing early treatment for liver cancer, it is important to prepare an animal model to evaluate cancer prevention treatment by using inflammation disease. The hepatocarcinogenic N-Nitrosodiethylamine (NDEA) has been reportedly able to produce free radicals that cause liver inflammation leading to liver carcinoma. This study aimed to evaluate the inflammation disease model of mice induced with hepatocarcinogenic NDEA for five weeks induction. Methods The BALB-c mice were induced with NDEA 25 mg/kg of body weight once a week for five weeks intraperitonially and it was then evaluated for the body weight during study periods. The mice were then sacrificed and excised for evaluating their organs including physical and morphological appearances and histopathology evaluations. Results The results showed a significant decrease of body weight of mice after five times induction of 25 mg NDEA/kgBW per week intraperitonially. Different morphological appearances and weight of mice organs specifically for liver and spleen had also been observed. The histopathology examination showed that there were hepatic lipidosis and steatohepatitis observed in liver and spleen, respectively that might indicate the hepatocellular injury. Conclusions It can be concluded that inducing mice with NDEA intraperitonially resulted in fatty liver disease leading to progress of cancer disease.

Ursolic acid (UA) is a pentacyclic triterpene carboxylic acid which produces various effects, including anti-cancer, hepatoprotective, antioxidant and anti-inflammatory. However, UA demonstrates poor water solubility and permeability. Niosomes have been reported to improve the bioavailability of low water-soluble drugs. This study aimed to investigate the protective action of UA-niosomes with chitosan layers against liver damage induced by N-Nitrosodiethylamine (NDEA). UA niosomes were prepared using a thin layer hydration method, with chitosan being added by vortexing the mixtures. For the induction of liver damage, the mice were administered NDEA intraperitoneally (25 mg/kgBW). They were given niosomes orally (11 mg UA/kgBW) seven and three days prior to NDEA induction and subsequently once a week with NDEA induction for four weeks. The results showed that chitosan layers increased the particle sizes, PDI, and ζ-potentials of UA niosomes. UA niosomes with chitosan coating reduced the SGOT and SGPT level. The histopathological evaluation of liver tissue showed an improvement with reduced bile duct inflammation and decreasing pleomorphism and enlargement of hepatocyte cell nuclei in UA niosomes with the chitosan coating treated group. It can be concluded that UA niosomes with chitosan coating improved the efficacy of preventive UA therapy in liver-damaged mice induced with NDEA.

Chronic disease can cause tissue and organ damage constituting the largest obstacle to therapy which, in turn, reduces patients’ quality-adjusted life-year. Degenerative diseases such as osteoporosis, Alzheimer’s disease, Parkinson’s disease, and infectious conditions such as hepatitis, cause physical injury to organs. Moreover, damage resulting from chronic conditions such as diabetes can also culminate in the loss of organ function. In these cases, organ transplantation constitutes the therapy of choice, despite the associated problems of immunological rejection, potential disease transmission, and high morbidity rates. Tissue regeneration has the potential to heal or replace tissues and organs damaged by age, disease, or trauma, as well as to treat disabilities. Stem cell use represents an unprecedented strategy for these therapies. However, product availability and mass production remain challenges. A novel therapeutic alternative involving amniotic mesenchymal stem cell metabolite products (AMSC-MP) has been developed using metabolites from stem cells which contain cytokines and growth factors. Its potential role in regenerative therapy has recently been explored, enabling broad pharmacological applications including various gastrointestinal, lung, bladder and renal conditions, as well as the treatment of bone wounds, regeneration and skin aging due to its low immunogenicity and anti-inflammatory effects. The various kinds of growth factors present in AMSC-MP, namely bFGF, VEGF, TGF-β, EGF and KGF, have their respective functions and activities. Each growth factor is formed by different proteins resulting in molecules with various physicochemical properties and levels of stability. This knowledge will assist in the manufacture and application of AMSC-MP as a therapeutic agent.

This study evaluated the cellular uptake and cytotoxicity of low permeable Ursolic acid (UA) on cancer cells using niosomes composed of span 60 and cholesterol. The results showed that the addition of chitosan increased particle sizes and ζ-potentials.The UA niosomes with chitosan layers had higher cytotoxicity in HeLa cells than without chitosan, however, there was no improvement observed for Huh7it cells. Moreover, chitosan layers improved the cellular uptake, which clathrin-mediated endocytosis may determine the cellular transport of UA niosomes. In conclusion, the addition of chitosan improved cellular uptake and cytotoxicity of UA niosomes in the HeLa cells.