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Epidermal growth factor receptor variant III (EGFRvIII) is the most common variant of the EGF receptor in many human tumors. This variant is tumor specific and highly immunogenic, thus, it can be used as a target for targeted drug delivery toward tumor cells. The major aim of this study was to develop an EGFRvIII-mediated drug delivery system by anti-EGFRvIII monoclonal antibody (MAb) conjugated to doxorubicin (Dox)-loaded nanostructured lipid carriers (NLC) to enhance the targeting specificity and cytotoxic effect of Dox on EGFRvIII-overexpressing cell line. In our study, Dox was chosen as a hydrophobic cytotoxic drug and drug-loaded nanostructured lipid carriers (Dox-NLC) was prepared by solvent emulsification/evaporation method. In order to conjugate anti-EGFRvIII MAb to Dox-NLC, DSPE-PEG2000-NHS (1,2-distearoylphosphatidylethanolamine-polyethylene glycol 2000-NHS) was used as a linker. Physicochemical characteristics of antibody conjugated Dox-NLC (MAb-Dox-NLC), including particle size, zeta potential, entrapment efficiency and in vitro Dox release were investigated. Cytotoxicity of MAb-Dox-NLC against NIH-3T3 and HC2 20d2/c (EGFRvIII-transfected NIH-3T3) cell lines was evaluated. The MAb-Dox-NLC appeared to enhance the cytotoxic activity of targeted NLC against HC2 20d2/c cells. The cellular uptake percentage of targeted NLC by HC2 20d2/c cells was higher than that of NIH-3T3 cells, indicating that EGFRvIII can specifically target HC2 20d2/c cells. In conclusion, anti-EGFRvIII MAb-targeted NLC may be considered as an effective nanocarrier for targeted drug delivery.

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Background. Hypertension as a major risk factor for cardiovascular diseases is among the leading causes of death worldwide. The relationship between elevated serum levels of liver enzymes and hypertension has been reported in limited studies, and to the best of our knowledge, there are no previous reports in the literature on this issue in the southeast of Iran. Our investigation aimed at evaluating the relation between ALT, AST, GGT, and ALP with hypertension in the Rafsanjan Cohort Study, a city in Kerman Province, Iran. Methods. In this cross-sectional study, we used data obtained from the Rafsanjan Cohort Study (RCS), as a part of the prospective epidemiological research studies in Iran (PERSIAN). The association of the liver enzymes levels with hypertension was investigated using the multivariable logistic regression models. Results. Among 9930 participants, the mean age (±SD) was 49.94 (±9.56) years, and 46.56% were men. The odds of abnormal blood pressure significantly increased along with the higher levels of ALT, GGT, and ALP which remained significant only for ALP after adjustment for all confounding variables in both males and females (OR in males: 1.36, 95% CI = 1.09–1.69, OR in females: 1.25, 95% CI = 1.01–1.54). In subjects with normal levels of ALT, AST, GGT, and ALP, dose-response increases were observed for abnormal blood pressure in both genders. Finally, we found that, among liver enzymes, only elevated ALP was significantly correlated with the odds of stage 1 hypertension and stage 2 hypertension for both genders. Conclusions. In subjects with normal levels of ALT, AST, GGT, and ALP, dose-response increases were observed for abnormal blood pressure in both genders. Increased serum ALP activity was positively associated with increased odds of hypertension in males and females. Therefore, increased ALP could be an early indicator of hypertension.