Preparation And Properties Research Of Specifically Targeted Identified Polymer Antitumor Drugs Carriers

At present, chemotherapy and radiotherapy are the basic method for treatment of cancers. Chemotherapy commonly used small molecule drugs such as doxorubicin, camptothecin, paclitaxel, and suppressor gene drugs(siRNA). The first time, the use of small molecule drugs will develop resistance, often leading to cancer treatment relapse. Followed by intravenous injection role in the body organs, cells and tissues, reducing the concentration of the drug at the original cancer cells and normal tissue damage is great. Therefore, it is necessary to synthesize a drug carrier capable of specifically recognizing effective into tumor cells and response to tumor environmental stimuli release drug system. In this paper, synthesis of the three specificity main- passive targeting and intelligent controlled release polymer carrying drugs system.1. Studies of bond acetal and hydrazone bond dual-pH stimulus response drug release Using RAFT agent(DMPA) controlled structure polymerization process and the molecular weight reducing dispersion polymerization under mild conditions(for example at 60 ?). Aggregation of acetal monomer-methacryloxypropyl-hydrazone bond-polyethyleneglycol-folic acid monomer(PTTMA-P(MA-Hydrazone-PEG)-PFA ?)were characterized using 1H NMR. Determination trimethoxybenzaldehyde UV absorption in the 292 nm for time simulation in vitro hydrolysis under different conditions pH, after 72 hours hydrolysis percentage reached 90%. Parcel doxorubicin(DOX) simulation in vitro drug release, drug encapsulation obtained was 56.5% drug loading was 18.43. Dynamic light scattering and transmission electron microscopy showed that the micelle size of about 107 nm. Cells(human cervical cancer cells; Hela) experiments showed that polymeric micelles have good biocompatibility and non-cytotoxic(cell viability? 91%). After loading doxorubicin had a higher inhibition rate(0.64 ug / mL) with free DOX inhibition rate(0.90 ug / mL) are close, and confocal microscopy imaging revealed micelles can accumulate into the cell. Therefore, having a folate-targeted and pH dual-stimulilate responsive polymer PTTMA-P(MA-Hydrazone-PEG)-PFA micelles expected to be good targeting drug carrier.2. Studies of pH-reduction dual stimuli-responsive drug release Redox and pH dual-responsive folate tumor targeting biodegradable micelles were developed based on block copolymer Poly(Methacryloyl-SS-3, 4, 5-Trimethoxybenzoic acid)-b-Hydrazone-(Ethylene glycol)-P(Folic acid) [P(MA-SS-TMOBA)-Hyd-PEG-PFA, Polymer ?]. The amphiphilic copolymers were subsequently self-assembled into nanosized micelles of 120 nm with disulfide-TMOBA and hydrozone bonds safely encapsulated in the core. DOX was loaded into P(MA-SS-TMOBA)-Hyd-PEG- PFA micelles at theoretical drug loading contents(DLC) of 28.57 wt. % with a drug loading efficiency(DLE) of 58.27%. Analog cells release shows only 17.97% of DOX at pH 7.4, 37 oC(physiological conditions) was released from DOX-loaded P(MA-SS-TMOBA)-Hyd-PEG-PFA micelles in 48 h. Doxorubicin release was significant increased at pH 5.0(64.05%) and pH 7.4, 10 mmol/l dithiothreitol(DTT)(72.22%) in 48 h. The drug release was further increased under 10 mmol/l DTT and pH 5.0 conditions, with 92.48% of DOX released in 48 h. Cell experiments showed that polymeric micelles have good biocompatibility and without cytotoxicity(cell viability> 90%). After loading doxorubicin had a higher inhibition rate(0.91?g / mL),which was approaching to free DOX(0.58?g / mL) for Hela cells, and confocal microscopy imaging revealed micelles can enter the cell, effectivelys to kill the tumor cell. Thus, DOX-loaded P(MA-SS-TMOBA)-Hyd-PEG-PFA micelles could potentially be used as a promising system for a redox and pH dual-triggered release of anti-cancer drugs in folate-receptor positive cancer cells.3. Studies of the pH-stimulation responsive block copolymers drugs release carriers Synthesis of poly(4- methacryloxy- aldehyde benzoate)- polyethylene glycol-poly folic acid [P(HBA-TMOBA)-PEG-PFA] amphiphilic block polymer. After micelles prepared uniform particle size 106 nm, electron micrographs show spherical. Wrap drug doxorubicin in vitro release simulate normal human cells in a similar environment, only 14.62% of the doxorubicin release, and in the condition in 48 hours pH5.0 release rate of 78.87%, relative to free doxorubicin containing folate-targeted drug-loaded polymeric micelles enhances the cumulative release of drug in the cancer cells. Cytotoxicity tests demonstrate polymer P(HBA-TMOBA)-PEG-PFA nano-micelles non-toxic to normal tissues and had higher activity to human cervical carcinoma(Hela) cells. Therefore this against human cervical cancer cells targeted specifically identified folic acid-responsive polymer drug carrier micelles can be a good drug carrier.