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@#The aims of this research were to constitute and evaluate one targeting anticancer co-delivery system for both micro-molecularchemotherapeutic drugs(docetaxel, DTX)and small interfering RNA(siRNA)expressed by COX-2. The nanoparticles composed of poly(D, L-lactide-co-glycolide)(PLGA)bearing disulfide-linkaged reducible polyethyleneimine(PEIss)covered by hyaluronic acid(HA). Meanwhile, HA-PEI-PLGA nanoparticles were prepared as control. Firstly, the solvent evaporation was used to the particles which exhibited a core-shell structure with a uniform size of 150-200 nm. The cumulative drug release in two kinds of PBS media(pH 7. 4 and pH 5. 0)during 72 hours indicated that DTX-loaded nanoparticles had sustained-release effect within 24 hours. The cumulative release of DTX of HRPSP NPs in PBS pH 5. 0 was 10%-25% more than that in PBS pH 7. 4, which demonstrated that favored release of DTX from nanoparticles could be achieved in acidic tumor microenvironment. Then, the highest transfection efficiency was observed after 14-16 h incubation at N/P ratio of 40/1. Following the saturation of CD44 receptor, the mean fluorescence intensity of HRPSP NPs from the cells decreased drastically in the case of saturation with free HA before. However, there existed no significance in the fluorescence of RPSP NPs between the cells with and without saturation with free HA, which indicated the nanoparticles′ targeting potential toward tumor cells. In the Western blot, the relative silencing efficiency of Bcl-2, bax, capase-3 and COX-2 mRNAprotein was calculated. In comparison to the control group, the silence efficiencies of bax and capase-3 were both significantly increased while that of Bcl-2 was evidently reduced, particularly in siCOX-2/HRPSP NPs group(P< 0. 01). The similar results were obtained in the silence efficiency of COX-2 protein in which the COX-2 quantity on mRNA and protein decreased. The results suggest that the nanoparticles could achieve the synergistic effect on the combinatorial delivery of siRNA and lipophilic anti-tumor drugs.
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ObjectiveTo prepare recombinant human basic fibroblast growth factor (rhbFGF) loaded magnesium-poly(D,L-lactide-co-glycolide) (Mg-PLGA) stent and to evaluate its angiogenesis effect in rat model of hindlimb ischemia.MethodsThe stent was prepared with spiral magnesium (Mg) and loaded with therapeutic agent rhbFGF and PLGA matrix.In vitro drug release study was carried out and the effect was evaluated using a standard animal model of rat hindlimb ischemia.A mechanical drill was conducted and the stent was implanted.The concentrations of Mg2+ in the muscle adjacent to the stent,rat plasma,urine and stools of the experimental animals were tested to analyze the degradation and metabolism of metal Mg.Immunohistochemical staining was performed to evaluate the angiogenesis effect of the stent.ResultsThe drug loaded in the stent could release continuously for about 4 weeks.The concentrations of Mg2+ in the rat plasma,urine and stools were within normal range.Immunohistochemical and quantitative analysis showed that the effect of Mg-PLGA-rhbFGF stent on angiogenesis of rat limb ischemia was better than that of the control group.ConclusionRhbFGF loaded MgPLGA stent could promote angiogenesis of rat limb ischemia,and it may provide theoretical basis for the critical patients suffered from lower limb ischemic disease.
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Objective: To prepare exenatide-loaded poly (lactic-co-glycolicacid)(PLGA) microspheres and to evaluate their release behavior in vitro. Methods: Exenatide-loaded PLGA microspheres were prepared by W/O/O method using PLGA as vectors. An HPLC approach was established to determine the content and in vitro cumulative release. The physicochemical characteristics of microspheres, including the mean diameter, morphology, drug entrapment efficiency and loading efficiency, were evaluated. Results: The prepared microspheres were well-shaped, with a mean diameter of (51.2±1.97) μm. The drug loading was (4.50±0.13)% and the encapsulation efficiency was (96.5±2.68)%. The first day burst release was (13.19 ± 1.39)% and the in vitro 28-day-cumulative-release was (88.6 ± 0.73)%. Conclusion: The W/O/O method is stable, controllable, and repeatable for preparing exenatide-loaded microspheres using biodegradable polymers PLGA as the vector; the microspheres yield a one-month continuous release and have a bright future in treatment of diabetes mellitus.