ABSTRACT
The drug delivery system with "gatekeeper" is designed to achieve a stable entrapment state of the payload under normal physiological conditions through the gatekeepers. With tumor microenvironment or stimulation of exogenous factors, the gatekeeper is detached or altered to promote the responsive release of the drug. In this paper, we focus on applications of stimuli-responsive linkages and stimuli-responsive groups, and review research progresses of drug delivery system with "gatekeeper" developed over the past 10 years.
ABSTRACT
OBJECTIVE: To study on characterization, irritation, the release mechanism and the elimination kinetics of Fraxini Cortex thermosensitive in-situ-forming eye gel (FC-ISG). METHODS: The non-membrane dissolution model was used to observe the release mechanism of FC-ISG. The stabilities of FC-ISG were investigated under following circumstances bright light, freeze test and accelerating test. Single-dose and multiple-dose irritations of FC-ISG were evaluated by draize test. The elimination kinetics of FC-ISG were analyzed by non-compartment model. RESULTS: FC-ISG showed good stability and non-stimulation to rabbit eyes. Drug release from FC-ISG was completely controlled by gel erosion, the release kinetics was coincided with zero-level release. AUC and MRT in FC-ISG group were significantly higher than those in control group (P<0.05). CONCLUSIONS: FC-ISG can improve the bioavailability of drug by prolonging the residence retention time of drug in cornea. FC-ISG shows a great potential in ocular application.
ABSTRACT
OBJECTIVE: To study the effects of 5-Fu combined with resveratrol (Res) on the growth and apoptosis of A431 and TE-1 cell lines and the underlying mechanism. To study the therapeutic effects of 5-Fu/Res combination on mouse skin papilloma chemically induced by DMBA/TPA. METHODS: The effects of 5-Fu/Res combination on the viability of cancer cells were evaluated by MTT assay, growth curves assay and LDH releasing assay. The inhibitory effect of combination of the two drugs was analyzed by the method of Chou and Talalay. Apoptoses of A431 and TE-1 were determined by inverted microscope and gel electrophoresis of DNA fragment analysis. Intracellular Ca2+ concentration was determined to study the underlying mechanisms of 5-Fu and Res on the apoptosis of cancer cells. The mouse skin papilloma model was established by DMBA and TPA, the expression of actived-caspase-3 in mouse skin was examined by immunohistochemistry. RESULTS: Combination of 5-Fu and Res decreased the median inhibitory concentration (IC50) to cancer cells remarkably. 5-Fu/Res combination showed a synergistic effect on apoptosis of A431 and TE-1 cells. Much more typical morphological changes of apoptosis and amount of fragmented DNA were observed in the cells treated with 5-Fu and resveratrol in combination than that in the cells treated with the agents alone. The increase of [Ca2+]i induced by 5-Fu/Res combination might be involved in the apoptotic induction. There was a significant decrease of the number of tumors after treatment with 5-Fu and Res in the tumor-bearing mice model. Active caspase-3 in the cells of mice skin was generated by 5-Fu in combination resveratrol was more effective than either alone. CONCLUSION: The 5-Fu/Res combination shows synergistic anti-tumor effects both in vitro and in vivo.