Objective To develop paclitaxel-loaded polymeric micelles from poly (ε-caprolactone)-poly (ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL),and to evaluate in vitro cytotoxicity as well as in vivo antitumor activity against EMT-6 tumor breast cell.Methods Paclitaxel-loaded polymeric micelles were prepared by thin-film hydration and ultrasonic method.The physical status of paclitaxel inside the polymeric micelles was investigated by differential scanning calorimetry (DSC).In vitro cytotoxicity of paclitaxel-loaded polymeric micelles against EMT-6 cell line was assessed by MTT assay.In vivo anticancer activity was evaluated against EMT-6 tumorbearing mice,with commercially available Taxol injection as control.Results Paclitaxel-loaded polymeric micelles exhibited homogeneous spherical shapes with apparent core-shell morphology.The average diameter of paclitaxelloaded polymeric micelles was 93 nm.DSC study indicated that paclitaxel was in solid amorphous state after being encapsulated in the polymeric micelles.In vitro cytotoxicity demonstrated that the cytotoxic effect of paclitaxelloaded polymeric micelles was lower than that of Taxol injection at the same paclitaxel content.Paclitaxel-loaded polymeric micelles showed greater tumor growth-inhibition effect in vivo on EMT-6 breast tumor in comparison with that of Taxol injection,with tumor growth inhibition of 85.79％ and 63.37％,respectively (P＜0.05).Conculsions The prepared paclitaxel-loaded polymeric micelles showed high anti-tumoral efficacy and low toxicity,and might have the potential to be developed as an effective anticancer drug-delivery system for cancer chemotherapy.

Polymersomes have attracted tremendous attention as novel drug delivery systems because of their unique and superior structure,tunable membrane properties,colloidal stability,and ability in encapsulating a broad range of both water soluble and insoluble substances.In this paper,preparation method and criteria for the formation of polymersomes,their structure and characterization as well as amphiphilic block copolymers for vesicle formation are addressed.Moreover,research progress on polymersomes as drug delivery system in the field of therapeutic and diagnostic applications are reviewed in this paper.

ObjectiveTo prepare paclitaxel-loaded nanoparticles (NPs),and to observe drug biodistribution after intravascular infusion of the NPs using a DispatchTM catheter into New Zealand rabbit abdominal aorta models.Methods Paclitaxel-loaded NPs were prepared by ultrasonication/emulsificcation/solvent evaporation technique using biodegradable poly (lactic-co-glycolic acid)(PLGA) as drug carrier.NP size and morphology was assessed by submicro-laser defractometer and scanning electron microscopy.In vitro release of paclitaxel from the NPs was performed by shaking in PBS at 37℃.The NPs was delivered into New Zealand rabbit abdominal aorta using a DispatchTM catheter.ResultsThe diameter of paclitaxel NPs was around 246 nm with very narrow size distribution.The NPs showed good spherical shape with smooth uniform surface.Paclitaxel loading in the NPs was about 19.06％ with encapsulation efficiency about 93.25％.The NPs maintained a sustained in vitro drug release for 30 days in PBS.After in vivo NP infusion,paclitaxel was detected in the vascular tissue around the infusion site and it retained in the site for 21 days.ConclusionPLGA nanoparticles as local drug delivery carrier showed great potential to maintain a high local drug concentration and prolonged drug resident time in animal model in vivo.

ObjectiveTo develop doxorubicine-loaded nanomicelles based on a type of novel starshaped 4-arm PLGA-PEG-NH2 amphiphilic block copolymers.Methods 4s-(PLGA-PEG-NH2) synthesized by 4s-PLGA and (H2N-PEG-NH2) according to N,N'-dicyclohexylcarbodiimide(DCC) condensation reaction was demonstrated by 1H NMR spectroscopy and gel permeation chromatography(GPC); DOX-loaded 4s-(PLGA-PEG-NH2) nanomicelles were self-assembled by doxorubicin(DOX) and 4s-(PLGA-PEG-NH2) via emulsion-solvent evaporation method and characterized in terms of morphology,particle size and size distribution,drug loading,encapsulation efficacy,cell uptake and cytotoxicity studies.Results4s-(PLGA-PEG-NH2) were capable of selfassembling intocore-shell nanomicelles structure and encapsulating DOX into their hydrophobic cores.The mean size of DOX-loaded 4s-(PLGA-PEG-NH2) was nanometer size; drug loading and encapsulation efficacy were around 7.5％ and 75.2％,respectively.Mean surface charge of the micelles was around -17.6 mV.In vitro cell uptake and cytotoxicity studies indicated that comparing to the DOX-loaded linear-(PLGA-PEG-PLGA)nanomicelles,DOX-loaded 4s-(PLGA-PEG-NH2) nanomicelles showed better performance in uptaking by HeLa cells and higher cytotoxicity to cancer cells.Conclusion4s-(PLGA-PEG-NH2) amphiphilic block copolymers can be successfully used in encapsulating DOX,self-assemblingcore-shell nanomicelles in aqueous solvent.Therefore,4s-(PLGA-PEG-NH2) copolymers can be considered as a promising drug carrier in effectively carrying hydrophobic drug,improving the efficacy while reducing the side effect.

ObjectiveThe aim of the present study was to investigate the incorporation of plasmid DNA (pDNA) onto a coronary stent by chemo-immuno-conjugation for achieving site-specific gene delivery.MethodsA gene eluting stent was fabricated by reacting with polyallylamine bisphosphonate (PAA-BP) to introduce amine reactive groups on the surface.Then an anti-DNA antibody was chemically coupled and pDNA was immunologically tethered on the stent surface.Radioactive-labeled antibody was used to evaluate binding capacity and stability.ResultsThe presence of amine groups on the modified stent surface was confirmed by XPS and AFM analysis.The isotope label assay indicated that the amount of antibody chemically linked on the stents was 15-fold higher than that of the control stent and its retention time was also significantly longer.ConclusionThe results suggested that a large amount of reactive amine groups were introduced on the PAA-BP modified 316L coronary stent surface.This study provide a potential metal surface modification method that could facilitate coupling and tethering of biological molecules such as anti-DNA antibody and plasmid DNA (pDNA) to achieve sustained and highly localized gene delivery for substrate-mediated gene transfection.

Objective To construct an injectable controlled delivery system of paclitaxel based on thermosensitive PCL1250-PEG1500-PCL1250 hydrogels. Methods A thermosensitive PCL1250-PEG1500-PCL1250 triblock copolymer was synthesized by ring-opening polymerization of e-CL using PEG (Mw=l 500) as the initiator and Sn(Oct)2 as the catalyst. The synthesized PCL1250-PEG1500-PCL1250 copolymers were characterized for their composition,structure, and molecular weight via 1H NMR and GPC techniques. A series of Paclitaxel loaded hydrogels with various predesigned hydrogel concentrations and initial drug loadings were prepared to investigate their gelation ability, in vitro drug release behavior and in vivo biodegradability. Results The results calculated from 1H NMR and GPC indicated that EG/CL ratio(1.55) was consistent with the initial feed ratio(1.6), which offered a strong proof to their composition and molecular structure. The thermosensitive PCL1250-PEG1500-PCL1250 hydrogels exhibited a desirable sol-gel transition ability within the concentration range of 15%-30%. The in vitro release rate of paclitaxel from the paclitaxel/PCL1250-PEG1500-PCL1250 hydrogels was controllable by altering the hydrogel concentrations and initial drug loadings. The PCL1250-PEG1500-PCL1250 hydrogels showed a good in situ gelation ability after subcutaneously injected into mouse back. The in situ formed hydrogels gradually degradated with time and almost disappeared after 45 days in vivo. Conclusion Both the controllable drug release behavior and promising biodegradability of this new thermosensitive PCL1250-PEG1500-PCL1250 hydrogels paved a way to develop a novel delivery system for paclitaxel.

BACKGROUND: Currently used poly (alkyl-cyanoacrylates) (PACA) produces aldehyde compound in its degradation, which is easily results in toxicity and stimulation to the body. Here, a novel TaxoI-PACA micell material was synthesized, which has broad application as a kind of liposolubility drug delivery carrier. OBJECTIVE: To verify the therapeutic efficacy of Paclitaxel-PECA micells for mouse breast cancer.METHODS: Paclitaxel drug delivery micells were prepared by a multi-emulsification technique and were characterized for size, drug loading capacity, and in vitro release. Bablc breast cancer model mice were randomly divided into the physiological saline, vacant control, paclitaxel positive control, and Paclitaxel-PECA micells with low-dose, medium-dose, and high-dose groups. Paclitaxel and PaclitaxeI-PECA micells were injected into the location of mouse breast cancer, and then the tumor inhibit rates were detected. RESULTS AND CONCLUSION: The mean diameter of Paclitaxel-PECA micells was 70 nm, with 19.89% loading amount of Paclitaxel. In vitro, micells maintained sustained release of Paclitaxel for 2 weeks. Compared with the physiological saline group, the PaclitaxeI-PECA micells group exhibited superior tumor inhibit effects with doses of 30, 60, and 90 mg/kg (P < 0.001 ), which was 68.49%, 77.03% and 81.87%, respectively. The results suggested that Paclitaxel-PECA micells material has excellent acceptability as sustained-release preparation for treating mouse breast cancer.

OBJECTIVE:To prepare an intramyocardial bilayered porous biodegradable drug delivery stent and to evaluate its effects on myocardial channel after transmyocardial revascularization (TMR).METHODS:A biodegradable drug delivery stent was prepared by using poly (ε-caprolactone) (PCL),bovine serum albumin (BSA)and poly (D,L-lactide-co-glycolide) (PLGA).The levels of BSA in stent and released in vitro were determined by the Coomassie brilliant blue assay.The mechanical strength of stent was tested by universal material testing machines.Porcine models of chronic myocardial ischemia were created to evaluate the effects of this stent on myocardial channel after TMR,RESULTS:Each bilayered porous stent could carry 10 mg BSA and release about 80% of BSA after 30 days.The stent diminished 80% of initial scale under the stress of 1.2 MPa.It could keep myocardial channel patency after TMR.CONCLUSION:An intramyocardial bilayered porous biodegradable drug delivery stent was successfully prepared.It could sustain the pressure from the heart and maintain myocardial channel patency after TMR.

Objective To prepare paclitaxel-loaded poly(ε-caprolactone)(PCL)/pluronic F68(F68)blend microspheres as a controlled release system. Methods Paclitaxel-loaded PCL/F68 blend microspheres were prepared by the oil-in water(O/W)emulsion/solvent evaporation method. Characterization of the microspheres followed to examine the particle size, the drug encapsulation efficiency, the surface morphology, in vitro release behavior and DSC analysis. In vivo antitumor activity of paclitaxel-loaded PCL/F68 blend microspheres was evaluated in mice bearing with hepatoma H22 cells ascites tumor. Results The results showed that the porous structure can be formed in the surface of PCL/F68 blend microspheres. Faster and controlled release of paclitaxel from PCL/F68 blend microspheres was achieved in comparison with the PCL microspheres. In animal tests, paclitaxel-loaded PCL/F68 blend microspheres showed the potent antitumor activity against hepatoma H22 cells in ascites tumor model. Conclusion The paclitaxel loaded PCL/F68 blend microspheres were found to own a faster release rate and a remarkably controlled release behavior.

Nanoparticule (NP) as a drug and gene carrier has shown great potential and has been widely studied. Due to its ultra-small size, NP can achieve intelligent delivery of drugs, such as deliver drug site-specifically to disease focus or targeted tissue, even into target cells. The carrier materials of NPs provide it with such advantages as shielding odor, long-term sustained releasing of drug, lowering uoxicity,extend biologic half life of drug and gene, etc. This review emphasizes the manufacturing techniques and application of nanoparticles as drug and gene delivery system.