The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt (PSS) as anionic layer and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs (4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of-57.8 mV. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs (4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.
Antineoplastic Agents, Phytogenic ; administration & dosage ; chemistry ; Benzylisoquinolines ; administration & dosage ; chemistry ; Cell Line, Tumor ; Drug Liberation ; Humans ; Lactic Acid ; chemistry ; Nanoparticles ; adverse effects ; chemistry ; metabolism ; Polyamines ; chemistry ; Polyglycolic Acid ; chemistry ; Polystyrenes ; chemistry ; Static Electricity

Animals ; Cell Line, Tumor ; Cell Survival ; drug effects ; Ferrosoferric Oxide ; adverse effects ; metabolism ; pharmacology ; Humans ; Liver ; chemistry ; drug effects ; Lung ; drug effects ; metabolism ; Magnetics ; Mice ; Nanoparticles ; adverse effects ; Spectrophotometry, Atomic

Silica nanoparticles (SNPs) are widely used in many scientific and industrial fields despite the lack of proper evaluation of their potential toxicity. This study examined the effects of acute exposure to SNPs, either alone or in conjunction with ovalbumin (OVA), by studying the respiratory systems in exposed mouse models. Three types of SNPs were used: spherical SNPs (S-SNPs), mesoporous SNPs (M-SNPs), and PEGylated SNPs (P-SNPs). In the acute SNP exposure model performed, 6-week-old BALB/c female mice were intranasally inoculated with SNPs for 3 consecutive days. In the OVA/SNPs asthma model, the mice were sensitized two times via the peritoneal route with OVA. Additionally, the mice endured OVA with or without SNP challenges intranasally. Acute SNP exposure induced significant airway inflammation and airway hyper-responsiveness, particularly in the S-SNP group. In OVA/SNPs asthma models, OVA with SNP-treated group showed significant airway inflammation, more than those treated with only OVA and without SNPs. In these models, the P-SNP group induced lower levels of inflammation on airways than both the S-SNP or M-SNP groups. Interleukin (IL)-5, IL-13, IL-1beta and interferon-gamma levels correlated with airway inflammation in the tested models, without statistical significance. In the mouse models studied, increased airway inflammation was associated with acute SNPs exposure, whether exposed solely to SNPs or SNPs in conjunction with OVA. P-SNPs appear to be relatively safer for clinical use than S-SNPs and M-SNPs, as determined by lower observed toxicity and airway system inflammation.
Animals ; Asthma/*chemically induced/pathology ; Female ; Inflammation/*chemically induced/pathology ; Interferon-gamma/analysis ; Interleukins/analysis ; Lung/drug effects/*pathology ; Mice, Inbred BALB C ; Nanoparticles/*adverse effects/chemistry ; Ovalbumin/adverse effects ; Polyethylene Glycols/adverse effects/chemistry ; Silicon Dioxide/*adverse effects/chemistry ; Surface Properties

OBJECTIVETo assess the effect and safety of nano-Amoni Paste (nmAP) in the treatment of children's anorexia (AR).

METHODSOne hundred and eighty patients of AR were assigned according to the randomized, double-blinded, double-simulated and parallel controlled principle to three groups, the treated group (TG), the positive control group (PCG) and the negative control group (NCG), 60 in each group. The patients in TG were treated by sticking 1.5 ml of nmAP on the acupoint of Shenque (Ren 8) once a day and orally taking placebo liquid 10 ml twice a day; those in PCG and NCG treated with sticking paste of placebo on Ren 8, and oral taking of Shanmai Jianpi Oral Liquid and placebo liquid respectively, 10 ml each time twice per day. The course of treatment for all was 10 days, all patients were treated for 2 courses.

RESULTSThe total effective rate and the effective rate on cardinal symptom in TG was 85.0% and 95.0% respectively, that in PCG 86.2% and 96.55% and in NCG 45.5% and 65.45%, respectively, showing significant difference between groups (P<0.05). Comparison of the clinical manifestation before and after treatment showed significant improvement in volume of food intake, appetite, complexion and reduction of restlessness symptom (P<0.05) in all three groups, and there was no adverse reaction found in them.

CONCLUSIONnmAP is an effective and safe remedy for treatment of Children's anorexia.

Acupuncture Points ; Amomum ; chemistry ; Anorexia ; physiopathology ; therapy ; Appetite ; drug effects ; Body Height ; drug effects ; Body Weight ; drug effects ; Child ; Child, Preschool ; Double-Blind Method ; Eating ; drug effects ; Female ; Humans ; Liposomes ; Male ; Nanoparticles ; Oils, Volatile ; administration & dosage ; adverse effects ; isolation & purification ; therapeutic use ; Ointments ; Phytotherapy ; Plant Extracts ; administration & dosage ; adverse effects ; therapeutic use ; Psychomotor Agitation ; physiopathology ; Treatment Outcome

The study aimed to examine the applicability of carbon nanoparticles as a tracer for lymph node mapping and the related factors of lymph node and No.8p subgroup metastasis in patients with gastric cancer. Clinical data of 50 patients with gastric cancer, who had not received treatment preoperatively and underwent gastrectomy in Department of Gastrointestinal Surgery, Wuhan Union Hospital, between October 2014 and August 2015, were retrospectively analyzed. These patients were found to have no distant metastasis preoperatively. Thirty-five out of 50 patients were subjected to lymphatic mapping technique using carbon nanoparticles as the tracer, and the rest 15 cases did not experience the lymphatic mapping and served as controls. The sensitivity, specificity, false positive rate and false negative rate were calculated according to the number of lymph nodes, and the staining and metastasis condition of lymph nodes. The diagnostic value of carbon nanoparticles on metastatic lymph nodes was evaluated. The relationship between the metastasis of lymph nodes or subgroup No.8p lymph nodes and clinicopathologic features was analyzed by χ-test or Fisher's exact test. All patients underwent D2 surgery (lymph node dissection including all the group 1 and group 2 nodes) plus the dissection of the subgroup No.8p lymph nodes. It was found that the average number of harvested lymph nodes in lymphatic mapping technique group (45.7±14.5) was greater than that in control group (39.2±11.7), but the difference was not significantly different (P=0.138>0.05). The success rate, the accuracy, sensitivity, specificity and false negative rate was 97%, 57%, 28%, 62% and 72% respectively. The metastasis of lymph nodes was correlated to the depth of cancer invasion (T stage) (P=0.004<0.05), and the metastasis of No.8p lymph nodes was correlated to the extent of lymph node involvement (N stage) (P=0.007<0.05). Six cases had lymph node metastasis in subgroup No.8p, and their TNM stages and clinical stages were as follows: T1N2M0 IIA, T3N3M0 IIIB, T4aN3M0 IIIC, T4aN3M0 IIIC, T4aN3M0 IIIC, and T4bN3M0 IIIC. In conclusion, our study indicated that carbon nanoparticles failed to show good selectivity for metastatic lymph nodes; the result of lymphatic mapping does not achieve a satisfactory performance; the incidence of lymph node metastasis may increase, accompanying with the increase of the depth of cancer invasion; No.8p lymph node metastasis tends to occur for gastric carcinoma patients with the extent of lymph node metastasis over N2 stage.
Adolescent ; Adult ; Aged ; Carbon ; Carcinoma ; diagnostic imaging ; pathology ; surgery ; Female ; Humans ; Lymph Nodes ; diagnostic imaging ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Nanoparticles ; administration & dosage ; adverse effects ; chemistry ; Sensitivity and Specificity ; Stomach Neoplasms ; diagnostic imaging ; pathology ; surgery

BACKGROUNDThe development of regenerative therapies using derivatives of embryonic stem (ES) cells would be facilitated by a non-invasive method to monitor transplanted cells in vivo, for example, magnetic resonance imaging of cells labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Although ES cells have been labeled with SPIO particles, the potential adverse effects of the label have not been fully examined. The objective of this study was to determine whether SPIO labeling affects murine ES cell viability, proliferation, or ability to differentiate into functional endothelial cells (ECs).

METHODSCross-linked iron oxide (CLIO, an SPIO) was conjugated with human immunodeficiency virus transactivator of transcription (HIV-Tat) peptides, and murine ES cells were labeled with either CLIO-Tat, CLIO, or HIV-Tat. After labeling, ES cells were cultured for 4 days and Flk-1(+) ES cells identified and sorted by immunocytochemistry and fluorescence activated cell sorting (FACS). Flk-1(+) cells were replated on fibronectin-coated dishes, and ECs were obtained by culturing these for 4 weeks in endothelial cell growth medium supplemented with vascular endothelial growth factor (VEGF). ES cell viability was determined using trypan blue exclusion, and the proportion of SPIO(+) cells was evaluated using Prussian blue staining and transmission electron microscopy. After differentiation, the behavior and phenotype of ECs were analyzed by reverse transcription-polymerase chain reaction, flow cytometry, immunocytochemistry, DiI-labeled acetylated low-density lipoprotein (AcLDL) uptake, and Matrigel tube formation assay.

RESULTSCLIO-Tat was a highly effective label for ES cells, with > 96% of cells incorporating the particles, and it did not alter the viability of the labeled cells. ECs derived from CLIO-Tat(+) ES cells were very similar to murine aortic ECs in their morphology, expression of endothelial cell markers, ability to form vascular-like channels, and scavenging of AcLDL from the culture medium.

CONCLUSIONSCLIO-Tat is a highly effective label for ES cells and does not adversely affect cell viability, differentiation, or behavior. CLIO-Tat could be a useful marker for the non-invasive monitoring of transplanted stem cells.

Animals ; Cell Differentiation ; drug effects ; Cell Line ; Cell Survival ; drug effects ; Embryonic Stem Cells ; cytology ; drug effects ; Endothelial Cells ; cytology ; drug effects ; Ferric Compounds ; chemistry ; Flow Cytometry ; Immunohistochemistry ; Mice ; Microscopy, Electron, Transmission ; Nanoparticles ; adverse effects ; chemistry ; Reverse Transcriptase Polymerase Chain Reaction

The novel paclitaxel-loaded nanopaticle through surface modification with didodecylmethylammonium bromide (DMAB) was prepared and its prevenative against neointimal formation in a rabbit carotid artery injury model was tested. Paclitaxel-loaded nanoparticles were prepared from oil-water emulsions using biodegradable poly (lactic acid-co-glycolic acid) (PLGA). Specific additive for surface conjugation was added after particle formation. To enhance arterial retention using a cationic surfactant, DMAB, was used. The size and distribution, surface morphology and surface charge of the paclitaxel-loaded nanoparticles were then investigated by laser light scattering, scanning electron microscope and zeta potential analyzer. The drug encapsulation efficiency (EE) and in vitro release profile were measured by high-performance liquid chromatography (HPLC). Balloon injured rabbit carotid arteries were treated with single infusion of the paclitaxel-loaded NP suspension and observed for 28 days. The inhibitory effects of vascular smooth muscle cell migration and proliferation were evaluated as end-point. The NPs showed spherical shape with diameter ranging from 200 to 500 nm. The negatively charged PLGA NPs shifted to positive after the DMAB modification. The in vitro drug release profile showed a triphasic release pattern. 28 days later, morphologic analysis revealed that the inhibitory effect of intima proliferation is dose-dependent, and the 30 mg x mL(-1) nanoparticle concentration suspension could completely inhibit proliferation of intima. Paclitaxel-loaded nanoparticles through surface modification with DMAB provide an effective means of inhibiting proliferation response to vascular injury in the rabbit.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; chemistry ; therapeutic use ; Carotid Artery Injuries ; etiology ; pathology ; prevention & control ; Catheterization ; adverse effects ; Delayed-Action Preparations ; Drug Compounding ; Drug Delivery Systems ; Female ; Hyperplasia ; prevention & control ; Lactic Acid ; chemistry ; Male ; Nanoparticles ; Nanotechnology ; Paclitaxel ; administration & dosage ; chemistry ; therapeutic use ; Particle Size ; Polyglycolic Acid ; chemistry ; Rabbits ; Tunica Intima ; injuries ; pathology