Orally Administered Halofuginone-Loaded TPGS Polymeric Micelles Against Triple-Negative Breast Cancer: Enhanced Absorption and Efficacy with Reduced Toxicity and Metastasis.

Background: Halofuginone (HF)-loaded TPGS polymeric micelles (HTPM) were successfully fabricated using the thin-film hydration technique. HTPM via intravenous injection have been demonstrated to exert an excellent anticancer effect against triple-negative breast cancer (TNBC) cells and subcutaneous xenografts. In the present study, we further explored the potential treatment effect and mechanism of orally administered HTPM alone and in combination with surgical therapy on TNBC in subcutaneous and orthotopic mouse models. Methods: Herein, the stability and in vitro release behavior of HTPM were first evaluated in the simulated gastrointestinal fluids. Caco-2 cell monolayers were then used to investigate the absorption and transport patterns of HF with/without encapsulation in TPGS polymeric micelles. Subsequently, the therapeutic effect of orally administered HTPM was checked on subcutaneous xenografts of TNBC in nude mice. Ultimately, orally administered HTPM, combined with surgical therapy, were utilized to treat orthotopic TNBC in nude mice. Results: Our data confirmed that HTPM exhibited good stability and sustained release in the simulated gastrointestinal fluids. HF was authenticated to be a substrate of P-glycoprotein (P-gp), and its permeability across Caco-2 cell monolayers was markedly enhanced via heightening intracellular absorption and inhibiting P-gp efflux due to encapsulation in TPGS polymeric micelles. Compared with HF alone, HTPM showed stronger tumor-suppressing effects in subcutaneous xenografts of MDA-MB-231 cells when orally administered. Moreover, compared with HTPM or surgical therapy alone, peroral HTPM combined with partial surgical excision synergistically retarded the growth of orthotopic TNBC. Fundamentally, HTPM orally administered at the therapeutic dose did not cause any pathological injury, while HF alone led to weight loss and jejunal bleeding in the investigated mice. Conclusion: Taken together, HTPM could be applied as a potential anticancer agent for TNBC by oral administration.

Optimization of Maduramicin Ammonium-Loaded Nanostructured Lipid Carriers Using Box-Behnken Design for Enhanced Anticoccidial Effect against Eimeria tenella in Broiler Chickens.

Maduramicin ammonium (MAD) is one of the most frequently used anticoccidial agents in broiler chickens. However, the high toxicity and low solubility of MAD limit its clinical application. In this study, MAD-loaded nanostructured lipid carriers (MAD-NLCs) were prepared to overcome the defects of MAD by using highly soluble nanostructured lipid carriers (NLCs). The formulation was optimized via a three-level, three-factor Box-Behnken response surface method. Then, the optimal MAD-NLCs were evaluated according to their hydrodynamic diameter (HD), zeta potential (ZP), crystal structure, encapsulation efficiency (EE), drug loading (DL), in vitro release, and anticoccidial effect. The optimal MAD-NLCs had an HD of 153.6 ± 3.044 nm and a ZP of -41.4 ± 1.10 mV. The X-ray diffraction and Fourier-transform infrared spectroscopy results indicated that the MAD was encapsulated in the NLCs in an amorphous state. The EE and DL were 90.49 ± 1.05% and 2.34 ± 0.04%, respectively, which indicated that the MAD was efficiently encapsulated in the NLCs. In the in vitro study, the MAD-NLCs demonstrated a slow and sustained drug release behavior. Notably, MAD-NLCs had an excellent anticoccidial effect against Eimeria tenella in broiler chickens. In summary, MAD-NLCs have huge potential to form a new preparation administered via drinking water with a powerful anticoccidial effect.

Genetic diagnosis of neonatal-onset seizures.

Many seizures in neonates are due to early-onset epilepsy, which is often difficult to diagnose, especially to explore the causes. Recently, the development of next-generation sequencing (NGS) has led to the discovery of a large number of genes involved in epilepsy. This may improve prompt detection of early-onset epilepsy in neonates. This study aimed at analyzing the genotype-phenotype correlations in neonates with seizures in a bid to improve the understanding of genetic diagnosis of early-onset epilepsy. Clinical features and prognosis of 15 children who underwent genetic testing having had unexplained seizures from February 2016 to May 2018 in Children's Hospital of Chongqing Medical University were analyzed retrospectively. The salient findings were: poor response to stimulus and abnormal electroencephalogram (EEG) in the initial period were observed in the group with concomitant genetic abnormalities. Despite the recent progress in genetic technology, molecular diagnosis for neonatal-onset epilepsy can be challenging due to genetic and phenotypic heterogeneities. However, some genotypes are associated with specific clinical manifestations and EEG patterns. Therefore, in-depth understanding of genotype-phenotype correlations would be useful to clinicians managing neonates with early-onset seizures.

Stacking faults enriched silver nanowires: facile synthesis, catalysis and SERS investigations.

A facile approach based on seed-mediated method for synthesis of stacking faults enriched Ag nanowires (SFEANWs) was successfully developed. SFEANWs were formed and attached onto the seed (α-Fe2O3/Au) surfaces through the reduction of AgNO3 by ascorbic acid (AA) in the presence of sodium polyacrylate (PAANa). Their length can be tuned with different concentrations of AgNO3 or PAANa. According to the effects of seeds and PAANa, the plausible growth mechanism of SFEANWs was discussed. The catalytic activity of SFEANWs comparing with fivefold twinned Ag nanowires (FFTANWs) was evaluated through reducing p-nitrophenol by NaBH4. The activation energy of the classical reaction catalyzed by SFEANWs was calculated through the Arrhenius equation. In addition, these SFEANWs exhibited excellent surface enhanced Raman scattering (SERS) activities due to the hot spots located in the cross of the twist wires. The detection limit of by SERS for 1,4-benzenedithiol (1,4-BDT) was estimated about 10(-7) mol/L.

The effect of triphenylphosphane on corrosion inhibition of benzotriazole at Ag electrode monitored by SERS in nonaqueous solution.

The corrosion inhibition behavior of benzotriazole (BTAH) on Ag electrodes and the influence of triphenylphosphane (pph(3)) were investigated by electrochemical method, in situ surface-enhanced Raman spectroscopy (SERS) and direct electrochemical synthesis of surface complexes in nonaqueous solution. The results indicated that the BTA(-) ion was coordinated to the Ag surface to form a highly cross-linked surface polymer complex of [Ag(BTA)](n), which suppressed the dissolution and oxidation of Ag effectively. The introduction of a neutral ligand of pph(3) blocked the surface coordination processes of BTAH with the Ag electrode. It resulted in a decrease of inhibition efficiency to Ag surface. The ligand of pph(3) played a negative role on the corrosion inhibition of BTAH to the Ag electrode. The SERS results were well consistent with the cyclic voltammetry and polarization curves measurements. For modeling, two different surface complexes were prepared in acetonitrile with and without pph(3) by direct electrochemical synthesis. A polymer-like complex of [Ag(BTA)](n) attached to the Ag surface was obtained in the absence of pph(3), which suppressed the dissolution and oxidation of Ag effectively. A new binuclear compound, Ag(2)(BTA)(2)(pph(3))(4), was produced in acetonitrile with pph(3) and the final coordination process occurred in solution leading to difficulties in forming a compact surface film, thus decreasing the corrosion inhibition efficiency of BTAH. The role of pph(3) and the mechanism were proposed.