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??OBJECTIVE To construct a tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier containing paclitaxel(BSA-LC/DOPE-PTX)for effective antitumor therapy. METHODS In vitro drug release study was conducted using dialysis method. The stability of BSA-LC/DOPE-PTX was studied by testing the aggregation of BSA-LC/DOPE-PTX in 50% human plasma. The cytotoxicity of drug-loaded nanocarrier against MCF-7 cells was evaluated by standard MTT assay. The subcellular localization and intracellular drug release behavior of BSA-LC/DOPE were evaluated by LSCM. RESULTS In vitro drug release study demonstrated that paclitaxel(PTX)was released from BSA-LC/DOPE in a pH-dependent manner. The stability study showed that there was no significant change, suggesting that the coupling BSA could increase the stability in plasma. The cellular inhibition of BSA-LC/DOPE-PTX with BSA targeting agents was greater than that of LC/DOPE-PTX. BSA-LC/DOPE facilitated the capacity of endosomal escape, and rapidly released the loaded agents into the cytoplasm under acid conditions in lysosomes. CONCLUSION BSA-LC/DOPE, as biocompatible, tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier, is a promising system for effective intracellular delivery of PTX to tumors with optimal anti-tumor efficacy.     

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??OBJECTIVE To prepare and evaluate the novel core-shell structural phospholipid-functionalized mesoporous silica nanoparticles (MSN-LP) modified with angiopep-2 (ANG-MSN-LP). METHODS Mesoporous silica nanoparticles (MSN) was synthesized by the modified Stober method. MSN-PTX was prepared by saturated solution adsorption method. ANG-MSN-LP was developed by selfassembly and film hydration method. By using dialysis bag method to investigate the in vitro drug release characteristics and MTT method to investigate the cytotoxicity on HBMEC and C6 cells. The transport ability and effects on cell cycle of the carrier was investigated by the BBB monolayer model. RESULTS MSN was synthesized with high specific surface area (S_BET, 425 m²??g^-1), cumulative pore volume (V_p, 0.37 cm³??g^-1) and pore size(3.5 nm). PTX was highly encapsulated (drug loading efficiency up to 11.1%) into MSN. Results of in vitro release showed that about 75.5% of PTX released from ANG-MSN-LP-PTX after 48 h and burst release was effectively reduced compared with MSN-PTX or PTX solution, indicating pronounced sustained-release characteristics. The good biocompatibility and low toxicity of ANG-MSN-LP were evaluated by HBMEC and C6 cells. The transport ratio was 2.49% for PTX, 2.72% for MSN-PTX, 4.45% for MSN-LP-PTX and 10.74% for ANG-MSN-LP-PTX respectively. In addition, ANG-MSN-LP-PTX showed a higher cell number of G2-M phase of 40.92??6.20%. CONCLUSION ANG-MSN-LP is a prospective targeting drug delivery system for therapy of brain glioma. Meanwhile, saturated solution adsorption method can increase the drug loading efficiency highly.
     

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??OBJECTIVE To prepare nano-micelles with amphiphilic self-assembly poly (ethylene glycol)-co-poly (propylene sulfide) (PEG-PPS) copolymer as carrier to study the release characteristics of tilianin and investigate its activity to against H9c2 cell apoptosis in vitro. METHODS An amphiphilic diblock PEG-PPS polymer was used as a carrier material to prepare the tilianin-containing nano-micelles by solvent evaporation. The morphology, particle size and distribution, drug loading and encapsulation rate and in vitro drug release behavior were characterized, H9c2 rat myocardial cell injury model was established by hypoxia/reoxygenation process. Using propranolol (Pro) as a positive control, the morphology of injured cardiomyocytes was observed by microscope. Cell proliferation and cell apoptosis was detected to evaluate the protective effect of blank micelles, tilianin and tilianin loaded nano-micelles on H9c2 cells induced by hypoxia/reoxygenation. RESULTS Tilianin-loaded nano-micelles was spherical with uniform particle size distribution. The drug loading was 3.82%. The average particle diameter of tilianin-loaded nano-micelles was 137 nm, polydispersity coefficient was 0.162 and the encapsulation efficiency was 91.45%. In vitro drug release studies showed that there was no drug-induced burst release of tilianin-containing nano-micelles and sustained release characteristics, and the presence of hydrogen peroxide significantly promoted the release of tilianin from the nano-micelles. In vitro cytotoxicity experiments showed that when the concentration of tilianin 5 ??g??mL^-1, the cell viability of tilianin-loaded nano-micelles was significantly higher than the corresponding concentration of tilianin and PEG-PPS polymer nano-micelles. In vitro anti-apoptotic activity experiments show that tilianin-loaded nano-micelles on H9c2 cell apoptosis induced by hypoxia-reoxygenation have a significant inhibitory effect and was provided inhibition of apoptosis with propranolol. CONCLUSION Tilianin-loaded nano-micelles have uniform particle size and distribution, sustained release and oxidation characteristics, has a significant protective and apoptosis-inhibiting effect on H9c2 cell injury induced by hypoxia-reoxygenation, which can be used as a promising drug delivery system for the treatment of myocardial ischemia-reperfusion injury.     

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??OBJECTIVE To prepare atorvastatin-loaded tetracycline-PEG-PLGA(TC-PEG-PLGA/ATO) polymeric micelles, and investigate its pharmaceutical characteristics and targeting function in vitro. METHODS The amphiphilic TC-PEG-PLGA conjugate was synthesized via an esterification reaction and identified by the ¹H-NMR. Water insoluble atorvastatin was loaded on TC-PEG-PLGA conjugate micelles via dialysis method. The morphology of TC-PEG-PLGA/ATO micelles was observed under transmission electron microscope. The particle size distribution and Zeta potential of TC-PEG-PLGA/ATO micelles were determined by dynamic light scattering method. The drug loading and encapsulation efficiency were measured by HPLC, and in vitro release behavior was investigated via dialysis method. In vitro cytotoxicity was assessed via MTT assay, and bone-targeting activity was investigated via binding to the hydroxyapatite powder. RESULTS TC-PEG-PLGA/ATO micelle was prepared successfully, and its particle size and Zeta potential were (47.2??4.7) nm and (-14.25??0.31) mV. The encapsulation efficiency and drug loading rate were(98.2??1.51)% and (8.71??0.23)%, respectively. Moreover, the accumulative release of ATO in vitro was about 70% in 48 h, which indicated that the drug was released slowly from the micelles. In vitro cell evaluation showed that TC-PEG-PLGA conjugate micelles were great biocompatibility with MC3T3-E1 cells within the concentration range of 100-500 ??g??mL^-1. In vitro targeting performance indicated that the proportion of the TC-PLGA NPs bound to Hap(87.94%) was greater than the bound proportion of PLGA NPs(18.59%). CONCLUSION The TC-PEG-PLGA/ATO micelles exhibit small partical size and good stability, and significantly increased ATO content in aqueous solution. TC-PEG-PLGA/ATO micelles have good delayed release behavior, safety and binding efficacy to the hydroxyapatite powder.     

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??OBJECTIVE To study the preparation of pluronic-modified biodegradable poly(butylene succinate) (PBSu) nanoparticles (NPs) and evaluate the release kinetics of the drug-loaded PBSu NPs and the cytotoxicity of the NPs, so as to provide a new platform for the application of biodegradable PBSu in drug delivery. METHODS Pluronic L61-modified PBSu NPs were prepared by emulsification method, and the morphology of the NPs was observed by transmission electron microscopy. The in vitro release kinetics of the rifampicin-loaded L61-PBSu NPs at 37 ?? was studied. The cytotoxicity of the L61-PBSu NPs against human ovarian cancer cells (OVCAR-3) was evaluated by MTT assay. RESULTS The drug-loaded NPs had a unimodal distribution with an average size of (140??7) nm. The drug encapsulation efficiency attained 64.98%. The release time reached 27 h when the cumulative release percentage was 90%. The release kinetics followed non-Fickian mechanism. The NPs demonstrated very low cytotoxicity against OVCAR-3 cancer cells. Modification by L61 improved biocompatibility. CONCLUSION The Pluronic-modified PBSu NPs are easy to prepare, biocompatible, and show great promise as a new passive targeting platform for controlled release of insoluble drugs.     

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??OBJECTIVE To prepare calcitonin/puerarin-PLGA-dual-loaded nanoparticles modified by chitosan, and investigate theirin vitro release behavior.METHODS CS-CT/PR-NPs were prepared by the double emulsion solvent evaporation technique with PLGA as a carrier material; the formulation of CS-CT/PR-NPs was optimized by orthogonal design; the morphology of CS-CT/PR-NPs was observed by transmission electron microscope;the mean particle size,particle size distribution and Zeta potential were measured by laser particle size analyzer; the entrapment efficiency and drug loading were measured by ultracentrifugation; the in vitro release behavior was studied by dialysis. RESULTS CS-CT/PR-NPs were spherical in shape with the mean particle size of(190??2.65) nm, particle size distribution of (0.117??0.027) and Zeta potentialof(16.5??1.08) mV. The entrapment efficiency was (75.7??1.15)%, and the drug loading of CT was (3.47??0.31)%, while those of PR were (50.9??1.08)% and (4.68??0.19)%, respectively. The profiles of in vitro release had the features of sustained-release. CONCLUSION CS-CT/PR-NPs are prepared successfully and show a sustained-release characteristic with high entrapment efficiency, which may improve the oral bioavailability of CT and provide the experimental reference for preparing the dual-loaded nanoparticles.     

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??OBJECTIVE To evaluate the effects of drug concentration and perfusion rate on the recoveries of self-made linear microdialysis probes for further ocular pharmacokinetic study. METHODS Brimonidine tartrate was selected as the model drug. The in vitro recovery was determined using positive dialysis and retrodialysis at different perfusion rates and drug concentrations. And the in vivo recovery was determined using retrodialysis method. RESULTS The microdialysis recoveries of brimonidine tartrate were inversely proportional to perfusion rate,while independent of drug concentration. The positive dialysis and retrodialysis recoveries in vitro were different at 1.0 ??L??min^-1, but no significant difference at 2.0 and 3.0 ??L??min^-1. The in vitro recoveries were greater than those in vivo. CONCLUSION The self-made microdialysis probe has stable recovery and can be used in ocular pharmacokinetic study of brimonidine tartrate.     

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??OBJECTIVE To improve the dissolution rate of fenofibrate (FNB) by using starch source mesoporous carbon (SMC) as a carrier and achieve controlled release of the drug by utilizing double-layer osmotic pump technology to improve the oral bioavailability. METHODS FNB was loaded into the mesoporous of NMS by adsorption method to prepare the drug loading system (FNB-SMC). Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXDR) were used to characterize the present state of the drug before and after being loaded. The dissolution rate of FNB-SMC was investigated by in vitro dissolution test, and the formulation of the double-layer osmotic pump tablets of FNB-SMC was optimized. The oral bioavailability of the self-made tablet was investigated by in vivo experiment in rabbits. RESULTS FNB existed in the mesoporous of SMC in an amorphous state. The in vitro dissolution test showed that NMS could significantly increase the dissolution rate of FNB, and the double-layer osmotic pump technology could achieve Zero-order release of the drug. The in vivo experiments showed that the oral bioavailability of the self-made tablets was significantly improved. CONCLUSION The combination of starch source mesoporous carbon carrier and double-layer osmotic pump technology prevente the burst effect and significantly improve the oral absorption of FNB.