ABSTRACT
Background and purpose: Locoregional infusion chemotherapy such as hepatic artery, or hepaticportal vein infusion is one of the most important treatments for hepatocelluar carcinoma. This study was aimed to investigate the distribution of fluorouracil(5-FU) in rat hepatoma, liver tissue and plasma after administrated by caudal vein or locoregional routes of hepatic artery, hepaticportal vein, and hepaticportal vein with ligated hepatic artery. Methods:Twenty-four tumor-bearing rats were divided into 4 groups randomly, and they were infused with 5-FU through peripheral vein(caudal vein), hepatic artery, hepaticportal vein or hepaticportal vein with ligated hepatic artery, which dose was 20 mg/kg. High performance liquid chromatography was adopted to measure the content of 5-FU in hepatoma, liver tissue and plasma, and the drug penetration rate among them were calculated. Results:The group of hepaticportal vein with ligated hepatic artery reached the highest concentrations of 5-FU in live tissue and hepatoma, which concentrations were (22.1±9.5)μg/g and (16.4±7.2)μg/g. Then was the hepatic artery group, and the concentration of the hepaticportal vein group in the hepatoma focus was much smaller than the former 2 groups, which was (8.9±3.7)μg/g. The peripheral vein group got the lowest concentrations both in the liver tissue and hepatoma, which were (9.4±3.7) and (4.3±2.2)μg/g. The concentrations of 5-FU in the plasma in the peripheral vein group, the hepatic artery group, the group of hepaticportal vein with ligated hepatic artery and the hepaticportal vein group were (26.8±12.5), (16.4±9.7), (15.9±10.1) and (14.9±8.5)μg/mL, which indicated that the drug concentrations of the latter 3 groups were much lower than the former group. The hepatoma/plasma penetration rate of 5-FU in the group of hepaticportal vein with ligated hepatic artery, the hepatic artery group, the hepaticportal vein group and the peripheral vein group were 103.47%, 92.94%, 59.58% and 16.08%. Conclusion: Compared to the peripheral venous bolus injection, locoregional infusion could significantly increase the concentrations of chemotherapy agent in hepatoma focus and liver tissue, and decrease the drug distributions in peripheral blood. And the infusion through hepaticportal vein with ligated hepatic artery and through hepatic artery reaches higher concentrations in the hepatoma focuses, which indicate that they are 2 practical and promising routes for the locoregional chemotherapy of hepatoma.
ABSTRACT
Objective To study the percutaneous permeability characteristic of podophyllotoxin (POD) ethosomes in vitro. Methods Excised SD-rat abdomen skin was used as penetration barrier. The steady penetration rate and the skin residual amount were calculated to evaluate the percutaneous permeability of POD from ethosomes, tinctures, liposome, 30% hydro-ethanolic suspension, mixture of drug and blank ethosomes, respectively. Results The skin residual amount of POD in the ethosomes group was 8.17 ug/cm2 in 12 h, higher than those in the other groups. In addition, the steady penetration rate of POD in the ethosomes group decreased significantly compared with those in the liposome group with POD loading being 0.5%, and the hydro-ethanolic suspension group (P < 0.05), while no obvious difference was seen among the ethosomes group and the other groups. Conclusion Higher skin residual amount and lower steady penetration rate are observed in the ethosomes group.
ABSTRACT
Objective: To investigate percutaneous permeability and skin irritation of gastrodigenin so as to provide the basis on the development of transdermal drug delivery formulations. Methods: The modified Franz diffusion cell method and the excised rat skin were used to evaluate the percutaneous permeability of gastrodigenin. The effects of various common-used solvents, transdermal enhancers, and particle carriers on the permeability of gastrodigenin were studied. The rabbit skin irritation test was used to evaluate the safety of gastrodigenin solutions and their gels. Results: Gastrodigenin was easy to permeate rat abdominal skin. The penetration rate constant (Js) was 134.1 μg/(cm2·h), and transit dose accumulated in 24 h was 3 mg/cm2. The solubility and permeability of gastrodigenin could be enhanced by 30% EtOH, so it was an ideal solvent for gastrodigenin. Improvement effects of the transdermal enhancers (Azone, turpentine, and borneol) and the transdermal particle carriers (microemulsion and ethosomes) were not significant. The skin irritation test results indicated that neither gastrodigenin soultions nor their gels exerted irritative effects to the rabbit skin. Conclusion Gastrodigenin has good percutaneous permeability without skin irritation, so it is suitable for the transdermal drug delivery in the treatment of central nervous system diseases.