چكيده به لاتين
In this thesis, the capability of anticancer drug, in tis case Doxurobicin (DOX), with block copolymer including poly{γ-2-[2-(2methoxyethoxy)ethoxy]ethoxy-3-caprolactone} (PMEEECL) and poly(β-amino ester) (PAE) which is responsive to both temperature and pH has been studied by means of molecular dynamics (MD) simulations. In this regard, PMEEECL with 20 repeating units in order to meet the experimental results was firstly performed by all-atom MD simulations. The lower critical solution temperature (LCST) or coil-to-globule transition temperature (Tcg) of PMEEECL was calculated around 320 K which is in good agreement with experimental results. Then, the effect of PMEEECL oligomer length was studied by all-atom MD simulation and the results showed transition temperature reduction by decreasing the repeating unit. Also, for pentamer there was no observable coil-to-globule transition by MD simulations. In order to DOX encapsulation, block copolymer which PAE was selected as the pH-sensitive polymer was used. As could be anticipated, adding hydrophobic block, i.e. PAE, changed the transition temperature of block copolymer PMEEECL20-PAEM and therefore the length of PAE block was altered from 5 to 15. The transition temperature of this block copolymer was achieved 315, 305, and 300 K for M = 5, 10, and 15, respectively. To study the micellization process, coarse-grained (CG) technique was performed, in this case MARTINI CG force field. In this section, we firstly investigated the morphology and straucture of amphiphilic micelle of PMEEECL20-PAEM with M = 5, 10, and 15 by CGMD simulations which spherical, cylindrical and bilayer micelles formed, respectively. Finally, by changing the concentration of DOX from 1 to 5 and 10 wt% of spherical micelle, the encapsulation process was investigated by CGMD simulations. The thermo-responsive behavior of PMEEECL-PAE block copolymer was studied by all-atom MD simulations and the effect of pH was studied by the self-consistence filed (SCF) theory which showed the transition temperature at 315 K and demicellization at pH lower than 5.4. These values confirmed that PMEEECL-PAE block copolymer is suitable for drug delivery application for cancer tumors.
