OBJECTIVETo prepare arsenic trioxide (As2O3)-loaded biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles (NPS) and evaluate the glomeration ability, appearance, structure, surface and release characteristics of the NPs.

METHODSWith PLGA as the carrier material, As2O3 NPs (As2O3-NPS) were prepared with the method of matrix and ultrasound emulsification. According to the criteria of the diameter of the NPs, drug loading (DL) and embedding ratio (ER), the process of NP preparation was optimized by scanning electron microscopy (SEM), ultraviolet spectroscopy (UV), and XPS.

RESULTSThe As2O3-NPS prepared were uniformly spherical with an average diameter of 210-/+23 nm, DL of 29.6% and ER of 82.1%. The drug release assay in vitro showed a sustained drug-release capacity of the preparation.

CONCLUSIONAs2O3-NPS may serve as a carrier of As2O3 to change the pharmacokinetics of As2O3 in vivo, allow slow drug release, and prolong the drug circulation time after intravenous injection, thereby producing better antitumor effects.

Arsenicals ; administration & dosage ; chemical synthesis ; pharmacokinetics ; Drug Carriers ; Nanoparticles ; Oxides ; administration & dosage ; chemical synthesis ; pharmacokinetics ; Particle Size ; Polyglycolic Acid

AIMTo prepare magnetoliposome (MLP) containing dextran-encapsulated magnetite (Fe3O4), and to examine its physicochemical properties and its in vivo behavior on ICR mice.

METHODSReverse phase evaporation method was used to formulate MLP and the Fe2+ concentration was measured by o-phenanthroline method. Then the basic properties of MLP and in vivo distribution were studied with the aid of 3H isotope as biomarker.

RESULTSThe mean diameter of MLP was 602.5 nm and the final concentration of encapsulated Fe3O4 was 88.1 mg x L(-1). Under natural conditions most of the MLP was taken up by spleen after the administration via tail vain, but its uptake was reduced under the magnetic field. There was a great difference in vivo distribution between the left and right lobes of the liver and the left and right kidneys in magnetic fields.

CONCLUSIONReverse phase evaporation method was utilized to prepare magnetoliposomes. The formulation was stable and encapsulated high amount of magnetite. The delivery system could be oriented to certain tissues under magnetic field and satisfying magnetic responsiveness was observed.

Animals ; Dextrans ; administration & dosage ; pharmacokinetics ; Drug Delivery Systems ; Female ; Ferrosoferric Oxide ; Iron ; administration & dosage ; pharmacokinetics ; Kidney ; metabolism ; Liposomes ; Liver ; metabolism ; Magnetics ; Male ; Mice ; Mice, Inbred ICR ; Nanotechnology ; Oxides ; administration & dosage ; pharmacokinetics ; Particle Size ; Spleen ; metabolism

A set of L-band electron spin resonance imaging (ESRI) equipment suitable for biological species was developed and an ESRI experiment model for viable skin samples was established. The mechanic process of nitroxide free radical TEMPO (2,2, 6, 6-tetramethyl-1-piperidinyloxy) penetrating through skin sample and the spin density distribution of TEMPO after it interacted with skin sample were detected by the developed ESRI method. Skin samples were extracted from mice back. The experimental samples were prepared by cutting the skin pieces into square shape of 2 x 2 cm2 and then the samples were divided into three groups by treating them with three different methods: Method A, simple treatment by simply cutting the hair; method B, 8% Na2S depilation treatment for 10 min; method C, 8% Na2S depilation and then 5% pancreatic digestion treatment for 2 hours. The liposoluble solvent DMSO (dimethyl sulfoxide) and distilled water were used as two kinds of solvent for the TEMPO liquor. The results indicated that the skin-penetration properties of TEMPO were significantly different among samples treated with different methods and the surface cornifin of skin offered remarkable resistance to TEMPO. The TEMPO liquor of water could hardly penetrate through skins, whereas about 20%-30% of the original TEMPO compounds that solved in liposoluble solvent DMSO could penetrate through the skin sample treated with method C after 16 hours of interaction. Furthermore, the penetration rate of TEMPO through the skin tissue was a strong time dependent process. The preliminary application results suggested that ESRI technique could provide an effective and applicable method for dynamically researching skin-penetration properties of some special kinds of materials such as paramagnetic compounds.
Animals ; Cyclic N-Oxides ; pharmacokinetics ; Dimethyl Sulfoxide ; chemistry ; Electron Spin Resonance Spectroscopy ; methods ; Free Radical Scavengers ; pharmacokinetics ; Mice ; Piperidines ; pharmacokinetics ; Skin Absorption ; physiology ; Skin Physiological Phenomena ; drug effects ; Spin Labels

OBJECTIVE: We wanted to compare the human neural stem cell (hNSC) labeling efficacy of different superparamagnetic iron oxide nanoparticles (SPIONs), namely, ferumoxides, monocrystalline iron oxide (MION), cross-linked iron oxide (CLIO)-NH2 and tat-CLIO. MATERIALS AND METHODS: The hNSCs (5x105 HB1F3 cells/ml) were incubated for 24 hr in cell culture media that contained 25 microgram/ml of ferumoxides, MION or CLIO-NH2, and with or without poly-L-lysine (PLL) and tat-CLIO. The cellular iron uptake was analyzed qualitatively with using a light microscope and this was quantified via atomic absorption spectrophotometry. The visibility of the labeled cells was assessed with MR imaging. RESULTS: The incorporation of SPIONs into the hNSCs did not affect the cellular proliferations and viabilities. The hNSCs labeled with tat-CLIO showed the longest retention, up to 72 hr, and they contained 2.15+/-0.3 pg iron/cell, which are 59 fold, 430 fold and six fold more incorporated iron than that of the hNSCs labeled with ferumoxides, MION or CLIO-NH2, respectively. However, when PLL was added, the incorporation of ferumoxides, MION or CLIO-NH2 into the hNSCs was comparable to that of tat-CLIO. CONCLUSION: For MR imaging, hNSCs can be efficiently labeled with tat-CLIO alone or with a combination of ferumoxides, MION, CLIO-NH2 and the transfection agent PLL.
Cells, Cultured ; Contrast Media/chemical synthesis/pharmacokinetics ; Cross-Linking Reagents/chemistry ; Ferric Compounds/chemistry/*pharmacokinetics ; Ferrosoferric Oxide/chemical synthesis/pharmacokinetics ; Gene Products, tat/chemistry ; Humans ; Iron/*pharmacokinetics ; Magnetic Resonance Imaging/methods ; Nanoparticles ; Neural Tube ; Oxides/*pharmacokinetics ; Phantoms, Imaging ; Polylysine/pharmacokinetics ; Spectrophotometry, Atomic ; Staining and Labeling/*methods ; Stem Cells/cytology/*drug effects/metabolism ; Time Factors ; Transfection

AIMTo study the pharmacokinetic process about the concentration in rat plasma of the alkaloids from processed seeds of Strychnos nux-vomica with RP-HPLC method.

METHODSHypersil BDS C18 column was used and the mobile phase consisted of acetonitrile-water at the flow rate of 0.8 mL.min-1. The UV detection wave length was 254 nm.

RESULTSThe concentration-time data of strychnine, brucine, strychnine N-oxide and brucine N-oxide were all in accordance with an open two-compartment model after i.v. alkaloids. Their parameters were as follows: T1/2 alpha were (8 +/- 5), (4 +/- 3), (6.2 +/- 1.7) and (3.0 +/- 0.8) min, T1/2 beta were (262 +/- 125), (416 +/- 131), (285 +/- 50) and (342 +/- 141) min, CL were (17 +/- 4), (21 +/- 12), (1.9 +/- 1.8) and (2.8 +/- 1.1) mL.min-1, Vc were (1.4 +/- 0.5), (1.7 +/- 1.1), (0.24 +/- 0.16) and (0.23 +/- 0.06) L.kg-1, Vd were (6.0 +/- 1.2), (12 +/- 7), (0.8 +/- 0.6) and (1.5 +/- 0.6) L.kg-1, AUC were (57,578 +/- 25,578), (35,240 +/- 15,616), (93,088 +/- 22,375) and (177,712 +/- 120,110) h.microgram.L-1, respectively.

CONCLUSIONThe method is a good reference for pharmacokinetics in human bodies.

Alkaloids ; isolation & purification ; pharmacokinetics ; Animals ; Cyclic N-Oxides ; isolation & purification ; pharmacokinetics ; Drugs, Chinese Herbal ; isolation & purification ; pharmacokinetics ; Female ; Hot Temperature ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Seeds ; chemistry ; Strychnine ; analogs & derivatives ; isolation & purification ; pharmacokinetics ; Strychnos nux-vomica ; chemistry ; Technology, Pharmaceutical ; methods

OBJECTIVE: To investigate the effect of smear layer on apical sealing ability in teeth obturated with mineral trioxide aggregate (MTA) Plus as retrofilling materials. METHODS: Fifty freshly extracted maxillary anterior teeth or premolars with single root canal were used in this study. All teeth were instrumented to master apical point 60# by using the stepback technique, obturated with lateral condensation technique, and then apical resected. A rootend cavity was then instrumented with an ultrasonic diamond-coated tip. Then the selected teeth were randomly and equally divided into two groups (n=25). In the experimental group (smear-), the teeth were irrigated with 0.17 g/L ethylenediaminetetraacetic acid (EDTA) to remove smear layer on the root-end cavity wall; in the control group (smear+), the teeth were irrigated with physiological saline. Five teeth were extracted to evaluate the cleanliness of root end cavity walls under a videomicroscope, respectively. The scanning electron microscope (SEM) evaluation was also performed for the presence of smear layer and open tubule. For the additional 40 teeth, the root-end cavities were filled with MTA Plus. The quantitative apical leakage of each teeth was evaluated by measuring the concentration of leaked sucrose in apical reservoir on 1, 7, 14, 21, 28, 35, 42, 49 and 56 days, respectively. The samples were stored at 37 °C and 100% humidity for 56 days. Statistical analysis was done with ANOVA for repeated measurement design data. RESULTS: Removal of the smear layer did not cause significantly less apical leaked sucrose than that when the smear layer was left intact for 56 days (P>0.05). There were statistically significant differences at the concentration of leaked sucrose among different observation time points (P<0.05). CONCLUSION It may be concluded that removing the smear layer may not be necessary in root-end cavities filled with MTA Plus.
Aluminum Compounds ; Calcium Compounds ; Dental Leakage ; Drug Combinations ; Edetic Acid ; Oxides ; Root Canal Filling Materials ; Root Canal Irrigants ; Root Canal Preparation ; Root Canal Therapy ; Silicates ; Smear Layer ; Sucrose/pharmacokinetics*

PURPOSE: To study the effect of systemic administration of phenyl-N-tert-butylnitrone (PBN) on the degeneration of photoreceptor cells in rd mice. METHODS: PBN was injected intraperitoneally into FVB/rd mice on postnatal days (P) 5 to 14 (group A), and P10 to 18 (group B). At days P14, 16, 18, 20 and 27, morphological changes and apoptosis were analyzed by staining with hematoxylin and eosin or DAPI. The effect of PBN on apoptosis was analyzed in retinal pigment epithelial (RPE) cells by the measurement of caspase-3 activity. RESULTS: In control and group B mice, the outer nuclear layer (ONL) of the retina was composed of 8-10 rows at P12, and rapidly decreased to one row at P18. In group A mice, the ONL was preserved with 5-7 rows at P18, and decreased to one row at P22. PBN inhibited caspase-3 activity in cultured RPE cells. CONCLUSIONS: PBN delayed, but did not block, the degeneration of photoreceptor cells in rd mice. PBN may exert its inhibitory effect during the early phase of photoreceptor cell degeneration.
Retinal Degeneration/*drug therapy/metabolism/pathology ; Pigment Epithelium of Eye/drug effects/metabolism/pathology ; Photoreceptors, Vertebrate/drug effects/metabolism/*pathology ; Nitrogen Oxides/*administration & dosage/pharmacokinetics/therapeutic use ; Neuroprotective Agents/*administration & dosage/pharmacokinetics/therapeutic use ; Mice ; Male ; Injections, Intraperitoneal ; Free Radical Scavengers/*administration & dosage/pharmacokinetics/therapeutic use ; Follow-Up Studies ; Female ; Enzyme Precursors/metabolism ; Disease Models, Animal ; Cells, Cultured ; Caspases/metabolism ; Caspase 3 ; Apoptosis/drug effects ; Animals

OBJECTIVETo evaluate the effect and adverse effects of arsenic trioxide (As2O3) in the treatment of primary hepatocarcinoma patients, and conduct the pharmacokinetics study.

METHODSA total of one hundred and eleven advanced primary hepatocarcinoma patients in five centers were treated with As2O3 injection 7 - 8 mg/m(2) i.v. qd for 14 days and was repeated after 7 - 14 days. Evaluation of the clinical response and adverse effects was conducted after two cycles of treatment. The patient who had reached partial PR and SD was treated continuously until disease progression or intolerance.

RESULTSAmong the 102 patients evaluable for clinical efficacy analysis, there were 7 PR, 71 SD and 24 PD, the response rate was 6.9% and the clinical benefit rate was 76.5%. The quality of life was improved in 22.5% of patients. The pain relief rate was 71.7%, time to progress (TTP) was 97 days, and the median survival time (MST) was 195 days. The major adverse effects were reversible WHO I-II grade gastrointestinal reactions and bone marrow suppression. The results of pharmacokinetic study showed that the distribution and elimination characteristics in vivo was found to be a two-compartment model. The plasma elimination half-life was (23.94 ± 18.39) h.

CONCLUSIONSAs2O3 is effective in the management of primary hepatocarcinoma, with a significant analgesic effect. To some extent, it can extend TTP and MST in advanced liver cancer patients, while the treatment is well tolerated in the majority of patients.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Arsenicals ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Carcinoma, Hepatocellular ; blood ; drug therapy ; pathology ; Disease Progression ; Female ; Follow-Up Studies ; Half-Life ; Humans ; Injections ; Leukopenia ; chemically induced ; Liver Neoplasms ; blood ; drug therapy ; pathology ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Oxides ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Quality of Life ; Remission Induction ; Survival Rate ; Vomiting ; chemically induced