| Therapeutic drugs have been widely used to treat disease for a long time. However, they were prone to get metabolized and their side effect was inevitable, which restricted their application in therapy.In this work, fristly, a new amphiphilic polymer octadecyl-quaternized modified poly (γ-glutamic acid) (OQPGA) were synthesized by poly (γ-glutamic acid) (γ-PGA) and octadecyl dimethylammonium chloride (QA). The solubility, zeta potential, critical micelle concentration (CMC) value and cytotoxicity were evaluated. Secondly, cationic polymeric liposomes (CPLs) were prepared by OQPGA and Cholesterol (Chol). Epidoxorubicin loaded PEG/RGD-MPLs (EPI/MPLs-PEG/RGD) were prepared by OQPGA, PEG modified OQPGA (PEG-OQPGA), RGD modified OQPGA (RGD-OQPGA) and magnetic nanoparticles and their strctures and performances were evaluated. Quantum dots loaded polymeric liposomes (QDs-CPLs) were prepared and their performances were studied. Lidocaine as a narcotic was encapsulated into CPLs and the performances of the formed local anesthetic were tested by in vitro and in vivo experiments. Thirdly, the core-shell system was developed by poly (lactide-co-glycolide) (PLGA), PEG-OQPGA, RGD-OQPGA, TAT modified OQPGA (TAT-OQPGA), Fe3O4 nanoparticles and Chol. The performances such as magnetic property, binding ratio of vector to gene, drug release profile, cellular uptake and cells transfection were evaluated.Results showed that, fristly, both FT-IR and 1H-NMR spectum indicated that OQPGA were synthesized successfully. OQPGA with various DS prepared in this work exhibited excellently solubility both in aqueous and organic media. The zeta potential of various OQPGA were positive, and they increased with the enhancement of DS. The CMC value of OQPGA was determined as about 0.05 mg/ml with a fluorescence spectrophotometer using pyrene as a fluorescence probe. The MTT analyses demonstrated that OQPGA did not cause signi?cant cytotoxicity against the GES-1 cell line below the concentration of 10 mg/L.Secondly, (1) the particle size of CPLs prepared by film dispersion method was larger than that of CPLs prepared by reverse phase evaporation method. The CPLs prepared by OQPGA and Chol (weigt ratio 2:1) exhibited smallest particle size and zeta potential and best stability in pH =7~8. (2) PEG-RGD-MPLs were multilamellar spheres with nano-size (50~70nm) and positive surface charge (28~42mV). Compared with magnetic conventional liposomes, EPI-MPLs-PEG/RGD exhibited sufficient size and zeta potential stability, low initial burst release and less magnetic nanoparticles leakage. The cell uptake results suggested that the EPI-MPLs-PEG/RGD exhibited more drug cellular uptake than non RGD and non magnetism carriers in MCF-7 cells. MTT assay revealed that MPLs-PEG/RGD showed lower in vitro cytotoxicity to GES-1 cells at ? 100 mg/L. (3) The size and zeta potential of the QDs-CPLs changed slightly when the solution buffer pH<9. Furthermore, QDs-CPLs exhibited high ?uorescence intensity and excellent photoluminescence stability in water and wide range of pH from 2 to 12. (4) Compared with lidocaine injection (2%) and lidocaine loaded conventional liposomes (2%), lidocaine loaded CPLs exhibited fast and good skin penetration in vivo.Thirdly, the core-shell system EPI/PLGA/MPLs-PRT was developed by PLGA, PEG-OQPGA, RGD-OQPGA, TAT-OQPGA, Fe3O4 nanoparticles and EPI. The formed core-shell system remained superparamagnetic and binding ratio of that to EGFP plasmid was 5:1. Compare with PLGA nanospheres, EPI/PLGA/MPLs-PRT /pEGFP exhibited excellent drug sustained release effect, higher cellular uptake, as well as good cell transfection in C6 tumor cell lines.In a word, delivery system based on CPLs represented a promising potential as an alternative multifunctional effective drug and gene delivery platform. |
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