The purpose of this study was to investigate the effects of vehicles, enhancers, and polymer membranes on 3'-azido-3'-deoxythymidine (AZT) permeation across cadaver pig skin. Four binary vehicles (ethanol/water, isopropyl alcohol/water, polyethylene glycol 400/water, and ethanol/isopropyl myristate [IPM]) were tested for AZT solubility and permeability across pig skin; ethanol/IPM (50/50, vol/vol) demonstrated the highest AZT flux (185.23 microg/cm2/h). Next, the addition of various concentrations of different enhancers (N-methyl-2-pyrrolidone [NMP], oleic acid, and lauric acid) to different volume ratios of ethanol/IPM was investigated for their effect on AZT solubility and permeability across pig skin. The use of 2 combinations (ethanol/IPM [20/80] plus 10% NMP and ethanol/IPM [30/70] plus 10% NMP) resulted in increased AZT solubility (42.6 and 56.27 mg/mL, respectively) and also high AZT flux values (284.92 and 460.34 microg/cm2/h, respectively) without appreciable changes in lag times (6.25 and 7.49 hours, respectively) when compared with formulations using only ethanol/IPM at 20/80 and 30/70 volume ratios without addition of the enhancer NMP. Finally, AZT permeation across pig skin covered with a microporous polyethylene (PE) membrane was investigated. The addition of the PE membrane to the pig skin reduced AZT flux values to 50% of that seen with pig skin alone. However, the AZT flux value attained with ethanol/IPM (30/70) plus 10% NMP was 215.31 microg/cm2/h, which was greater than the target flux (208 mug/cm2/h) needed to maintain the steady-state plasma concentration in humans. The results obtained from this study will be helpful in the development of an AZT transdermal drug delivery system.

BackgroundPancreatic cancer is considered a rare type of cancer, but the mortality rate is high. Cannabinoids extracted from the cannabis plant have been interested as an alternative treatment in cancer patients. Only a few studies are available on the antitumor effects of cannabinoids in pancreatic cancer. Therefore, this study aims to evaluate the antitumor effects of cannabinoids in pancreatic cancer xenografted mouse model.Materials and MethodsTwenty-five nude mice were subcutaneously transplanted with a human pancreatic ductal adenocarcinoma cell line (Capan-2). All mice were randomly assigned into 5 groups including negative control (gavage with sesame oil), positive control (5 mg/kg 5-fluorouracil intraperitoneal administration), and cannabinoids groups that daily received THC:CBD, 1:6 at 1, 5, or 10 mg/kg body weight for 30 days, respectively. Xenograft tumors and internal organs were collected for histopathological examination and immunohistochemistry.ResultsThe average tumor volume was increased in all groups with no significant difference. The average apoptotic cells and caspase-3 positive cells were significantly increased in cannabinoid groups compared with the negative control group. The expression score of proliferating cell nuclear antigen in positive control and cannabinoids groups was decreased compared with the negative control group.ConclusionsCannabinoids have an antitumor effect on the Capan-2-derived xenograft mouse model though induce apoptosis and inhibit proliferation of tumor cells in a dose-dependent manner.

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