This review presents the most outstanding contribution in the field of polymeric nanoparticles used as targeting drugs delivery systems. Nanoparticles barrier is a novel kind of controlled release system for drugs which can effectively deliver the drug to a target site and increase the bioavailability and therapeutic benefit, while minizing the side effects. In this paper the applications of nanoparticles in the active, passive and physical targeting drugs carriers are reviewed.
Albumins ; administration & dosage ; Antibodies, Monoclonal ; administration & dosage ; Biological Availability ; Cyanoacrylates ; administration & dosage ; Drug Carriers ; Drug Delivery Systems ; Humans ; Nanotechnology ; Particle Size ; Polymers ; administration & dosage

AIMTo prepare recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) -loaded stealth nanoparticles with different PEG chain lengths and sizes, and investigate the stability of nanoparticle suspensions.

METHODSThe poly( MePEG cyanoacrylate-co-hexadecyl cyanoacrylate) (MePEG-PHDCA) and poly(hexadecyl cyanoacrylate) (PHDCA) were synthesized and characterized with Fourier transform infrared spectrum (FTIR), 1HNMR, 13CNMR and gel permeation chromatography (GPC). Uniform design was used to optimize the entrapment efficiency. The nanoparticle suspensions were stored at 2 - 8 degrees C for 4 weeks, and the particle size evolution was studied.

RESULTSFTIR, 1HNMR and 13CNMR were consistent with the structures of MePEG-PHDCA and PHDCA whose polydispersity indexes were all less than 1.1, indicating narrow distributions. The entrapment efficiency of all nanoparticles was satisfactory. The three different mean diameters of MePEG-PHDCA and PHDCA nanoparticles were about 80 nm, 170 nm and 240 nm, separately. The nanoparticle suspensions maintained their sizes at 2 - 8 degrees C for 4 weeks

CONCLUSIONMePEG-PHDCA with three different molecular weight MePEG and PHDCA were synthesized successfully. There are negligible aggregations and bulk or surface erosion as for both stealth MePEG-PHDCA and conventional PHDCA nanoparticles in distilled water.

Cyanoacrylates ; chemistry ; Drug Carriers ; Drug Delivery Systems ; Drug Stability ; Humans ; Nanotechnology ; Polyethylene Glycols ; chemistry ; Recombinant Proteins ; administration & dosage ; Tumor Necrosis Factor-alpha ; administration & dosage

A 12-week-old baby with a vein of Galen aneurysmal malformation (VGAM) was successfully treated with performing transarterial microcatheter-directed embolization with Berenstein Liquid Coils and n-butyl cyanoacrylate in the feeding arteries. Post-procedure angiography showed a marked decrease of the blood flow into the dilated vein of Galen. Three months later, follow-up angiography showed that the vein of Galen aneurysmal malformation had totally disappeared, and the baby recovered very well without any sequelae. We report here on this interesting case along with a review of the relevant literature, and we aim to enhance physicians' awareness of the treatment for VGAMs.
Catheterization/*instrumentation ; Cerebral Angiography ; *Cerebral Veins ; Cyanoacrylates/*administration & dosage ; Embolization, Therapeutic/*instrumentation/methods ; Humans ; Infant ; Intracranial Arteriovenous Malformations/diagnosis/*therapy ; Magnetic Resonance Imaging ; Male

A 52-year-old male with right carotid body tumor underwent direct percutaneous glue (n-butylcyanoacrylate [NBCA]) embolization. Several hours later, he developed left hemiparesis from embolization of the polymerized glue cast. Migration of glue during percutaneous tumor embolization is presumed to occur only in the liquid state, which may lead to stroke or cranial nerve deficits. To the best of our knowledge, this is the first report of delayed glue embolization from a treated hypervascular tumor of the head and neck.
Carotid Body Tumor/blood supply/*therapy ; Cyanoacrylates/administration & dosage/*adverse effects ; Embolization, Therapeutic/*methods ; Enbucrilate ; Foreign-Body Migration/*complications ; Humans ; Injections, Intralesional ; Male ; Middle Aged ; Stroke/*etiology

AIMPoly (methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate) (PEG-PHDCA) and PHDCA niosomes were prepared and the influence of the PEG chain length on the niosomes physicochemical characteristics, complement consumption and phagocytic uptake were studied.

METHODSThe physicochemical parameters of PEG-PHDCA niosomes were characterized in terms of particle size, zeta aqueous layer thickness. The relationship between physicochemical characteristics and in vitro complement consumption and phagocytic uptake was further illustrated.

RESULTSExperimental results showed that PEG10,000-PHDCA had most loose structure and least PEG surface density among three groups. Configuration simulation through fixed aqueous layer thickness confirmed that PEG folding and less flexibility of the PEG chains of PEG10,000-PHDCA niosomes were accountable for its poor stealth effects. Compared with PEG2,000-PHDCA, PEG5,000-PHDCA showed a thicker fixed aqueous layer (FALT) of 4.20 nm, less negative zeta potential of -10.03 mV, and enhanced PEG surface density of 0.49 PEG x nm(-2), leading to the best effects of reduction of complement consumption and phagocytic uptake.

CONCLUSIONExcessive chain length of PEG was not necessary for stealth effects of PEG-PHDCA niosomes. PEG5,000-PHDCA niosomes had best effects on evading complement consumption and subsequent phagocytic uptake.

Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; Camptothecin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Complement System Proteins ; metabolism ; Cyanoacrylates ; chemical synthesis ; chemistry ; Drug Carriers ; Macrophages ; physiology ; Male ; Mice ; Particle Size ; Phagocytosis ; Polyethylene Glycols ; chemical synthesis ; chemistry ; Surface Properties

AIMTo investigate the influence of particle size and methoxypolyethyleneglycol (MePEG) molecular weight on the in vitro macrophage uptake and in vivo long circulating of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha)-loaded stealth nanoparticles in rats.

METHODSThree sizes (approximately 80, 70 and 240 nm) of poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles loading rHuTNF-alpha were prepared at different MePEG molecular weights (Mr 2,000, 5,000, 10,000) using the double emulsion method. The in vitro macrophage uptake and in vivo long circulating properties in rats were examined and compared.

RESULTSThe uptake by macrophages decreased and the half-life of rHuTNF-alpha in rat increased with the increase of MePEG molecular weight or the decrease of particle size. The linear-ships between particle size and MePEG molecular weight and the in vitro macrophage uptake and in vivo long circulating properties were fairly good. Having the highest MePEG surface density (1.32 nm(-2)) , the shortest average distance between neighboring MePEG chain (0.87 nm) and the thicker fixed aqueous layer thickness (FALT, 5.16 nm), PEG5,000-PHDCA nanoparticles (80.0 nm) earned the strongest potency of decreasing uptake by macrophages and prolonging the half-life of rHuTNF-alpha in rat.

CONCLUSIONWithin the experimental limits, particle size and MePEG molecular weight had dramatic influence on in vitro macrophage uptake and in vivo long circulating properties of rHuTNF-alpha-loaded stealth nanoparticles.

Animals ; Cyanoacrylates ; chemistry ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Macrophages ; physiology ; Male ; Mice ; Molecular Weight ; Nanoparticles ; Particle Size ; Phagocytosis ; drug effects ; Polyethylene Glycols ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; pharmacokinetics ; Tumor Necrosis Factor-alpha ; administration & dosage ; pharmacokinetics

A novel amphiphilic copolymer, folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL) was synthesized as liposomal modifying material with folate receptor targeting and long circulating property. FA-PEG-PCHL-modified docetaxel-loaded liposomes (FA-PDCT-L) were prepared by organic solvent injection method, and the system was optimized using central composite design-response surface methodology. The structure of the FA-PEG-PCHL copolymer was confirmed by FT-IR and 1H NMR. Ultrafiltration technique, transmission electron microscope, dynamic light scattering and electrophoretic light scattering, and fluorescence polarization method were used to study the physicochemical parameters of FA-PDCT-L. FA-PDCT-L showed spherical or ellipsoid shape. The mean particle sizes were in the range of 111.6-126.9 nm, zeta potentials were from -6.54 mV to -14.13 mV and the drug encapsulation efficiency achieved 97.8%. The observed values agreed well with model predicted values. The membrane fluidity increased with the increment of the molecular weight of PEG and the decrement of the amount of FA-PEG-PCHL. The in vitro release test showed that the drug could be sustained-released from liposomes without a burst release and with stability for 6 months. After 24 h only 31.1%, 27.2% and 19.5% of encapsulated docetaxel were released for FA-PDCT10000-L, FA-PDCT4000-L and FA-PDCT2000-L, respectively. This work is useful for further research on the application of the synthesized copolymer-modified long circulating liposomes for cancer therapy.
Antineoplastic Agents ; administration & dosage ; Cholesterol Esters ; chemistry ; Cyanoacrylates ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; chemical synthesis ; chemistry ; Drug Delivery Systems ; Folate Receptors, GPI-Anchored ; chemistry ; Liposomes ; administration & dosage ; chemistry ; Molecular Weight ; Particle Size ; Polyethylene Glycols ; chemistry ; Polymers ; chemical synthesis ; chemistry ; Taxoids ; administration & dosage

Intravariceal injection of N-butyl-2-cyanoacrylate is widely used for the hemostasis of bleeding gastric varices, but not routinely for esophageal variceal hemorrhage because of various complications such as pyrexia, bacteremia, deep ulceration, and pulmonary embolization. We report a rare case of esophageal sinus formation after cyanoacrylate obliteration therapy for uncontrolled bleeding from post-endoscopic variceal ligation (EVL) ulcer. A 50-year-old man with alcoholic liver cirrhosis presented with hematemesis. Emergent esophagogastroscopy revealed bleeding from large esophageal varices with ruptured erosion, and bleeding was initially controlled by EVL, but rebleeding from the post-EVL ulcer occurred at 17th day later. Although we tried again EVL and the injections of 5% ethanolamine oleate at paraesophageal varices, bleeding was not controlled. Therefore, we administered 1 mL cyanoacrylate diluted with lipiodol and bleeding was controlled. Three months after the endoscopic therapy, follow-up endoscopy showed medium to large-sized esophageal varices and sinus at lower esophagus. Barium esophagography revealed an outpouching in esophageal wall and endoscopic ultrasonography demonstrated an ostium with sinus. It is noteworthy that esophageal sinus can be developed as a rare late complication of endoscopic cyanoacrylate obliteration therapy.
Cyanoacrylates/administration & dosage/*adverse effects ; *Embolization, Therapeutic ; Endoscopy, Digestive System ; Esophageal and Gastric Varices/complications/*diagnosis/therapy ; Esophagus/radiography/ultrasonography ; Ethiodized Oil/therapeutic use ; Gastrointestinal Hemorrhage/surgery/*therapy ; Humans ; Ligation ; Liver Cirrhosis, Alcoholic/*complications/diagnosis ; Male ; Middle Aged ; Tissue Adhesives/administration & dosage/*adverse effects ; Ulcer/*complications

The anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomes (FA-PDCT-L) was investigated in vitro and in vivo. FA-PDCT-L was prepared by organic solvent injection method. Transmission electron microscope, dynamic light scattering and electrophoretic light scattering were employed to study the physicochemical parameters of FA-PDCT-L. The inhibitory effects of docetaxel injection (DCT-I), non-modified DCT liposomes (DCT-L) and FA-PDCT-L on the growth of MCF-7 and A-549 cells at different incubation times were detected by CCK-8 assay; and the hemolytic test was employed in vitro. Tumor mice were randomized into 4 groups: DCT-I, DCT-L, FA-PDCT-L and control group (normal saline), and given drugs at 10 mg x kg(-1) x d(-1) through tail vein. The tumor volume, mice weight, inhibition rate of tumor and life span were measured at the end of experiments. The IC50 of the FA-PDCT-L for MCF-7 and A549 cell lines were significantly lower than that of DCT-I and DCT-L, without hemolysis reaction observed. Compared with control group, the weights of tumor in DCT-I, DCT-L and FA-PDCT-L were decreased, especially for FA-PDCT-L, with inhibitory rates at 79.03 % (P < 0.05). The life span and median survival time of FA-PDCT-L treated mice were significantly higher than that of DCT-I and DCT-L. In conclusion, FA-PDCT-L shows a good anti-tumor activity, indicating that it is potential carriers for DCT in the treatment of tumor.
Animals ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyanoacrylates ; chemistry ; Drug Carriers ; Female ; Folate Receptors, GPI-Anchored ; chemistry ; Humans ; Inhibitory Concentration 50 ; Liposomes ; chemistry ; Lung Neoplasms ; pathology ; MCF-7 Cells ; Mice ; Neoplasm Transplantation ; Particle Size ; Polyethylene Glycols ; chemistry ; Rabbits ; Random Allocation ; Sarcoma 180 ; pathology ; Taxoids ; administration & dosage ; pharmacology ; Tumor Burden ; drug effects