Steered Mole cular Dynamics Sim ulation of Adriam ycin Dr ug Uptake by N-iso propylacrylamide Copolymers

Therm oresponsiv e polymers, which are usually fo rmed by am phiphilic c opolymers, have attracted growing interestdue to their trem endous potential applications in m edicine especially as ve hicles for drug deli very. Poly(N-isopropylacrylamide) (P-NIPA M) is a t ypical thermosensitivepo lymeric material, which exhibits a reversiblethermoresponsive phase transition in an aq ueous solution andaround the lower critical solution temperature (LCST) (it is۳۲ƕC for pure P-NIPAM) [۱–۲]. Based on the LCS T behavior, several P-NIPAM-conta ining block copolymers have been used as a n oveldrug ca rrier in the f ield of drug target. When P-NIPAM forms the hydrophilic shell of the micell e, the drug is released and exhibi ts its bioactivity for a ti me period u pon local heating. The simplicity of the micelle formed by self-assembly of amphiphilic bloc k copolymers and the drug encapsulations by physical mixi ng are extrem ely attractive features of polymeric micelles. Adriamycin (Doxorubicin, ADR) is an active medicine a gainst many cancers. It is most commonly used in the treatm ent of neop lastic diseases, but the unmodified ADR rapidly releases from the liposome uponintravenous injection while to o many doses could cause side effects [۳]. Therefore, it is necessa ry to develo p the safe and efficient drug c arriers that can deliver ADR exc lusively without provoking adverse reactions in disease therapy. S everal P-NIPAM-cont aining polymeric micelles have been adopted to reduce adv erse drug re actions.In this work, ap plying mol ecular dynam ics (MD) and considering two molecules: poly(N-isopropyla crylamide)-b lock-poly(ethylene glycol) and (N -isopropylacrylamide-co acrylic acid), we can st udy the stru cture and ch emical prop erties of stability, diffu sion and binding energy between m olecules. The MD is wi dely used in drug design to study the three-dimensiona l propertie s and inter action energies of molecules, and can be u sed in sim ulation stu dies, etc. Thus, predictive comp utational mo dels can be used to accelerate the selection process of lead compoun ds to deliver drugs fro m large pol ymer libraries prior to synthesis and biological characteri zation [۴].

کلیدواژه ها:

Molecular model ، Drug copolymers ، Force FIeld ، Adriamycin ، T hermoresponsive polymers