| Doxorubicin (DOX) is an antitumor anthracycline that represents the first-line therapeutic option in many hematological and solid tumors, but acute and chronic administration can produce serious cardiotoxicity. In order to reduce toxicity and increase the selectivity, the effective measures have been put into the development the drug delivery system.In this paper, we utilized natural protein-Zein which is biocompatible and biodegradable as carrier material to prepare DOX in situ gel drug delivery system used for interstitial chemotherapy. This drug delivery system was similar to target drug administration. DOX-Zein in situ gel was originally injected as a liquid and then formed a semisolid agent which sustained the release of DOX and enhanced bioavailability obviously.The Microcosmic structures of Zein and in situ gel were analyzed by Small Angle X-ray Scattering(SAXS), optical microscope and scanning electron microscope. The results showed that Zein in the solvent Glycerol formal was a pentamer form and the mechanism of in situ gel release was inferred. Prescription by screening was carried out by means of in vitro release study, viscosity and sedimentation measurement then obtained the optimal prescription. The results showed that mixture of Glycerol formal and alcoholic became the solvent and only Zein was made as carrier. Murine lung cancer tumor model was established and microdialysis method was utilized to monitor the in vivo drug release. The results showed that the in situ gel could sustain the effect of the drug for at least 7 days. In vitro antitumor activity research was carried out with the WST-1 assay; and in vivo pharmacodynamics was proceeded by means of inhibition tumor curve, suggesting that in situ gel group was superior to DOX solution group.
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