Abstract:
Doxoruicin (DOX) is a commercial and widely used anticancer drug. Nevertheless it also has certain severs side effects. In order to minimize these detrimental effects, various drug delivery systems, including polymer-drug delivery systems have been developed. It has been demonstrated that a chitosan-based delivery system, especially in nanoparticles, can reduce such side effects and extend the release time. Therefore, this thesis develops new drug delivery systems for doxorubicin in order to enhance adhesion between tumor tissues and the drug, giving an opportunity for the drug to contact with the cancer tissues for a longer period of time. moreover, it may increase drug metabolism in cancer cells and control drug release during the required time. The nanoparticles of chitosan and 4-carboxybenzenesulfonamide-chitosan with poly (lactic acid) by the electrospray technique were studied. In preliminary study, the effects of electrospray factors on the shape and size distribution have been investigated, including needle gauge, applied voltage, flow rate and working distance. In addition, the physical properties such as the surface morphology, particle size distribution, Fourier transformed infrared spectroscopy (FTIR), Differential scanning caorimetry (DSC), Thermogravimetric analysis (TGA), encapsulation efficiency, and in vitro release behavior were investigated. The composite polymer-doxorubicin nanoparticles produced high entrapment efficiency and gave the prologed release profiles of doxorubicin. The release profiles of doxorubicin were greatly improved upon using modified-chitosan with the increasing ratio of poly (lactic acid). Overall, it was clearly shown that the formulation of 2.0% doxorubicin loaded composit modified-chitosan/poly (lactic acid) at the ratio of 1:2 could provide controlled release for 26 days. Moreover, the (m-CS/PLA)-DOX (1:2 w/w)-2% showed the most potent inhibition of topoisomerase II enzyme (78.69%inhibition).
