The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery

Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.     

Thermodynamic and Kinetic Binding Behaviors of Human Serum Albumin to Silver Nanoparticles

A nanoparticle, under biological milieu, is inclined to be combined with various biomolecules, particularly protein, generating an interfacial corona which provides a new biological identity. Herein, the binding interaction between silver nanoparticles (AgNPs) and human serum albumin (HSA) was studied with transmission electron microscopy (TEM), circular dichroism (CD), and multiple spectroscopic techniques. Due to the ground state complex formed mainly through hydrophobic interactions, the fluorescence titration method proved that intrinsic fluorescence for HSA was probably statically quenched by AgNPs. The complete thermodynamic parameters were derived, indicating that the interaction between HSA and AgNPs is an entropy-driven process. Additionally, synchronous fluorescence and CD spectrum results suggested the conformational variation it has upon binding to AgNPs and the α-helix content has HSA visibly decreased. The kinetic experiments proved the double hysteresis effect has in HSA’s binding to the AgNPs surface. Moreover, the binding has between HSA and AgNPs follows the pseudo-second-order kinetic characteristic and fits the Freundlich model for multilayer adsorption. These results facilitate the comprehension about NPs’ underlying biological effects under a physiological environment and promote the secure applications of NPs biologically and medically.     

羧甲基壳聚糖复合纳米银、纳米氧化铜的制备及抑菌性研究

本研究在水热条件下利用羧甲基壳聚糖分别还原硝酸银和硫酸铜,得到稳定的羧甲基壳聚糖复合纳米银和纳米氧化铜,并测试其抑菌能力.表征测试显示,所制的纳米银为20～30 nm的球状结构,纳米氧化铜为80～100 nm的花瓣状结构,二者都均匀稳定地分布于羧甲基壳聚糖中.抑菌试验显示,不同浓度的羧甲基壳聚糖复合纳米银(A组2 mg...     

Tie2基因对纳米金颗粒进入牙周组织的影响

目的 研究Tie2基因表达对不同粒径纳米金颗粒（gold nanoparticles, GNPs）进入牙周组织及停留情况的影响。方法 采用实时定量PCR和Western印迹法检测Tie2基因和蛋白在正常和转基因小鼠牙周组织中的表达;冰冻切片检测GFP在牙周组织中相对高表达的部位;小鼠尾静脉注射1g/kg剂量20、40、60、80nm粒径GNPs,应用ICP-AES技术检测牙周组织Au含量。结果 转基因小鼠比正常小鼠Tie2基因的表达高约2.5倍。Tie2蛋白在转基因小鼠牙周组织中显著高表达,差异具有统计学意义（P<0.05）。GFP荧光提示Tie2在转基因小鼠牙周组织血管周围表达相对较高。转基因小鼠和正常小鼠牙周组织中GNPs的累积量随粒径增大而减少,正常小鼠牙周组织中GNPs的累积量明显高于转基因小鼠,差异具有统计学意义（P<0.05）。结论 Tie2基因高表达不利于GNPs扩散。     

胰岛素壳聚糖纳米粒的制备

 目的制备胰岛素壳聚糖纳米粒。方法采用酶水解和超滤膜分离技术，得到不同相对分子质量的壳聚糖，由凝胶渗透色谱法测定其相对分子质量；采用溶剂扩散法制备纳米粒，研究纳米粒的空间结构，测定其粒径、表面电位(zeta电位)、模型药物胰岛素包封率及体外释放。结果通过控制酶水解条件，经超滤分离得到3种不同相对分子质量的壳聚糖，凝胶渗透色谱法测得的重均相对分子质量(MW)分别为10 289，41500和101 870。经溶剂扩散法制备得到的壳聚糖纳米粒，呈类圆形球体，粒径分布较窄，且随制备工艺中乙醇加入量的增加、分散用超声次数的增多，以及壳聚糖分子量的降低，粒径变小。壳聚糖纳米粒带正电荷，zeta电位值大于+30 mV。放射免疫法测得的药物包封率为72.66%。在壳聚糖酶存在条件下，前1 h体外释放药物较快，1 h后趋于平稳，并能持续释放6 h。结论选用合适相对分子质量壳聚糖制备胰岛素壳聚糖纳米粒，方法简便，药物包封率高，并有一定的缓释作用。     

The American Physician in Occupational Medicine and Hygiene

The satisfactory quality of the practice of occupational medicine in industry is essential to the safety and health of employees. Measures of environmental control are not, in themselves, a satisfactory means of protecting workmen against many common hazards of industrial operations. Careful surveillance of workmen by trained, experienced, and competent occupational physicians is essential in the prevention of illness and disability induced by occupational operations, materials, and types of energy. The professional responsibilities of the occupational physician extend beyond the industrial facility into the general environment where the escaping production materials, by-products, and wastes may penetrate, and also into the larger community where its products may be distributed. The gross inadequacy in the number of trained physicians in the professional field must be met before this urgent problem of national health can be solved.     

Ultrasonic resonator technology as a new quality control method evaluating gelatin nanoparticles

Nanomedicine is a quickly evolving field where more and more possible applications become evident and start entering clinical trials or even the market. However, the analytic methods are not always able to keep pace with the new formulations’ demands. One example of a promising medical implementation is oligodeoxynucleotide (ODN) delivery by gelatin nanoparticles (GNPs). Currently, quality control is dependent on either some time consuming or destructive spectrometric, chromatographic or electrophoretic methods. A possible enlargement of the portfolio by Ultrasonic Resonator Technology (URT) is investigated here by subjecting plain GNPs in various sizes and concentrations as well as ODN-loaded GNPs to URT analysis. If calibrated by photon correlation spectroscopy (PCS) and other spectroscopy methods for each single nanoparticle system parameter, URT is an efficient and non-destructive technique and serves as a broad characterization method. URT is emphasized to play a possible future part in the size, concentration and ODN loading monitoring, e.g. of gelatin nanoparticles in the course of formulation development.     

DNA–chitosan nanoparticles improve DNA vaccine-elicited immunity against Newcastle disease virus through shuttling chicken interleukin-2 gene

In this study, pCAGG-ChIL2 plasmid DNA containing the chicken interleukin-2 (ChIL-2) gene was used to prepare DNA–chitosan nanoparticles (CNPs). The CNPs prepared were spherical, with mean diameters between 100 and 200?nm, have a positive surface charge, and could protect DNA against DNase I degradation. The CNPs prepared were successfully used to transfect the Df-1 cell line with almost no cytotoxicity. CNPs prepared at an amino group to phosphate group ratio (N/P ratio) of 16 provided the highest transfection efficiency (1.1%) in medium with a pH of 6.5. When pCAGG-ChIL2 CNPs were administered to chickens simultaneously with a DNA vaccine against Newcastle disease virus (NDV), haemagglutination inhibition antibody titers and serum interferon-γ (IFN-γ) levels were significantly higher than in chickens immunised with the NDV DNA vaccine alone (p?<?0.05). The results demonstrate that pCAGG-ChIL2 CNPs improve DNA vaccine-elicited immunity against NDV challenge.     

Enhancing and targeting nucleic acid delivery by magnetic force

Insufficient contact of inherently highly active nucleic acid delivery systems with target cells is a primary reason for their often observed limited efficacy. Physical methods of targeting can overcome this limitation and reduce the risk of undesired side effects due to non-target site delivery. The authors and others have developed a novel means of physical targeting, exploiting magnetic force acting on nucleic acid vectors associated with magnetic particles in order to mediate the rapid contact of vectors with target cells. Here, the principles of magnetic drug and nucleic acid delivery are reviewed, and the facts and potentials of the technique for research and therapeutic applications are discussed. Magnetically enhanced nucleic acid delivery – magnetofection – is universally applicable to viral and non-viral vectors, is extraordinarily rapid, simple and yields saturation level transfection at low dose in vitro. The method is useful for site-specific vector targeting in vivo. Exploiting the full potential of the technique requires an interdisciplinary research effort in magnetic field physics, magnetic particle chemistry, pharmaceutical formulation and medical application.     

Gold: Hepatotoxic and cholestatic reactions

Summary Gold hepatotoxicity is an uncommon but significant clinical problem. Hepatitis was first manifested one day to four weeks after the last dose of gold at a cumulative range of 35 to 2900 mg. An interesting dichotomy was noted between cholestatic and hepatotoxic reactions. Hepatotoxic reactions were associated with other clinical signs of hyper-sensitivity, thus facilitating differential diagnosis from viral hepatitis. Sudden clinical improvement in a patient receiving gold should stimulate evaluation for a hepatotoxic reaction.