Enhanced Antitumor Efficacy of Curcumin-Loaded PLGA Nanoparticles Coated with Unique Fungal Hydrophobin.

Modifications to the surface chemistry, charge, and hydrophilicity/hydrophobicity of nanoparticles are applicable approaches to the alterations of the in vivo fate of intravenously administered nano-sized drug carriers. The objective of this study is to investigate the in vitro and in vivo antitumor efficacies of curcumin PLGA nanoparticles in relation to their surface structural modification via self-assembling coating with unique fungal hydrophobin. The hydophobin-coated curcumin PLGA nanoparticles (HPB PLGA NPs) were obtained by simply soaking curcumin-loaded PLGA nanoparticles (PLGA NPs) in aqueous fungal hydrophobin solution. The in vitro drug release behavior of the HPB PLGA NPS was also tested. The cytotoxicity and cellular uptake of these nanoparticles were determined in HepG2, A549, and Hela cell lines using MTT assay method and CLSM observation. The in vivo antitumor activity was evaluated in Hela tumor xenografted mice model. Compared with the PLGA NPs, the size and zeta potential of the nanoparticles were changed after hydrophobin coating, whereas similar in vitro release pattern was observed. The pharmacodynamics study showed prolonged blood retention of both nano-formulations than that of free curcumin, but no significant difference between the hydrophobin coated and uncoated nanoparticles. It was found that HPB PLGA NPs had increased cytotoxicities, higher cellular uptake, and improved antitumor efficacy. Surface modification of nanoparticles via self-assembling of hydrophobin is a convenient and promising method of changing particle surface physiochemical properties and antitumor performances. Further investigations, especially on tissue distribution, were needed to assess the potential application of the hydrophobin self-assembling coating in nano-drug delivery carriers.

Anti-Melanoma Activity of Single Intratumoral Injection of ZnPc Micelles Mixed With in situ Gel in B16 Bearing Mouse.

Photodynamic therapy (PDT) is a potential treatment strategy for melanoma. As a second-generation photosensitizer, Zinc phthalocyanine (ZnPc) has many advantages for anti-tumor PDTs, such as strong absorption in the red and near infrared regions, high photo and chemical stability, etc. However, ZnPc has a poor water solubility and is apt to aggregate due to the π-π interaction between molecules, which limits its applications. In this study, various solvents and surfactants were screened for dissolving ZnPc and preparing ZnPc@SDC-TPGS micelle and thermosensitive in situ gel. After the cytotoxic effects of thermosensitive gels on PDT were tested, the antitumor effects on PDT of them in mice by intratumoral injection were evaluated, including body weight, and tumor weight, volume and morphology. The cell death pathway and the relationship of reactive oxygen species yield with apoptotic rate of tumor cells induced by ZnPc in situ gel were investigated. The results were that N-methyl-pyrrolidone (NMP) mixed with 2 % SDC and aqueous solution containing 2 % TPGS and 2 % SDC were used to synthesize ZnPc@SDC-TPGS micelle and the thermosensitive in situ gel. The cytotoxic effects of thermosensitive gels showed good tumor suppression of ZnPc@SDC-TPGS in situ gel and no toxicity of the blank gel. Intratumoral injection in situ gel containing 3 µg ZnPc under irradiation demonstrated good tumor inhibition in mice with melanoma. Apoptosis has been established as the primary pathway of cell death, and the production of reactive oxygen species (ROS) plays a crucial role in cellular apoptosis induced by ZnPc@SDC-TPGS in situ gel. In conclusion, the intratumoral injection of ZnPc@SDC-TPGS thermosensitive in situ gel provides a promising local treatment option for melanoma.

Efficacy and safety of interferon α-2b spray for herpangina in children: A randomized, controlled trial.

OBJECTIVES: The treatment of acute herpangina is inconsistent. We aim to evaluate the effectiveness and safety of interferon α-2b spray versus Ribavirin for this disease. METHODS: A randomized, controlled trial was conducted in eight hospitals in China between 2016 and 2018. 668 patients (1-7 years old) were randomized into an experimental group (treated with Interferon α-2b spray) or control group (received Ribavirin Aerosol). Body temperature returning to normal within 72 h and remaining so for 24 h was the primary outcome; release of oral herpes and adverse events were the secondary outcomes. RESULTS: (1) The average age of onset was 2.5 years old. (2) After 72 h treatment, body temperature of 98.5% patients in experimental group and 94.3% in control group returned to normal and remained so for 24 h (P = 0.004). The differences were greater at 48 h treatment (95.2% vs. 85.9%, P < 0.001) and at 24 h (77.5% vs. 66.5%, P = 0.001). (3) The rate of improved oral herpes in the experimental group was higher than that in control group (46.7% vs.37.1%, P = 0.011). No adverse reaction occurred. CONCLUSIONS: Local application of recombinant interferon α-2b spray showed better efficacy for acute herpangina in children. It was safe for use.

[The distribution of azidothymidine palmitate galactosylated liposomes in mice].

Hepatocytes act as a reservoir for the human immunodeficiency viruses (HIV) and are responsible for its continual dissemination in the peripheral circulation. For this reason, galactosylated liposomes (GalLs) containing home-made [(2-lactoylamido) ethylamino] formic acid cholesterol ester (CH-ED-LA ) as a homing device were prepared to study the biodistribution of the liposomal azidothymidine palmitate (AZTP) in mice. Four liposomes of the present study, soybean phosphatidylcholine (SPC)/cholesterol(CH)/CH-ED-LA (80 : 10: 10, 10% GalLs), SPC/CH/CH-ED-LA (80 : 15:5, 5% GalLs), SPC/CH/CH-ED-LA (80 : 17 : 3, 3% GallLs) and SPC/CH (80 : 20, CL) incorporated AZTP were prepared by ethanol-injection method followed by ultrasonic-dispersion and characterized by entrapped efficiency which was more than 95% and their mean diameter was less than 100 nm, respectively. The effects of the addition upon the liposomal membrane potential and AZTP content were also unseen. The distributions of AZT in various organs were determinated by reversed phase HPLC after intravenous administration via tail vein in mice, at a dose of 15.85 mg x kg(-1) AZT solution and 30 mg x kg(-1) AZTP (at equimolar doses) in CL or GalLs, respectively. Compared to AZT control solution, the half-life of AZT in each group of AZTP liposomes increased significantly (P < 0.05). In addition, the concentration-averaged overall drug targeting efficiency (r(e)) of the liver presented by AZTP CL and GalLs containing 3% , 5% , 10% (mol/mol) CH-ED-LA increased 1.32 and 1.48, 2.13, 1.50 times as that of AZT solution, respectively. These results indicate that liposomes containing such novel galactosylated lipid, CH-ED-LA, had remarkably improved the targetability of AZTP to liver, and are anticipated to be a potential candidate for liver targeting delivery carriers.

Synthesis of a novel galactosylated lipid and its application to the hepatocyte-selective targeting of liposomal doxorubicin.

This paper described the synthesis of a novel galactosylated lipid with mono-galactoside moiety, (5-Cholesten-3beta-yl) 4-oxo-4-[2-(lactobionyl amido) ethylamido] butanoate (CHS-ED-LA), and the targetability of doxorubicin (DOX), a model drug, in liposomes containing 10% mol/mol CHS-ED-LA (galactosylated liposomes, GalL) to the liver was studied. The weighted-average overall drug targeting efficiency (Te(*)) was used to evaluate the liver targetability of GalL DOX. The results showed that GalL DOX gave a relatively high (Te(*))(liver) value of 64.6%, while DOX in conventional liposome (CL DOX) only gave a (Te(*))(liver) value of 21.8%. In the liver, the GalL DOX was mainly taken up by parenchymal cells (88% of the total hepatic uptake). Moreover, preinjection of asialofetuin significantly inhibited the liver uptake of GalL DOX (from 70 to 12% of the total injected dose). It was suggested that liposomes containing such novel galactosylated lipid, CHS-ED-LA, had a great potential as drug delivery carriers for hepatocyte-selective targeting.

Self-assembly multifunctional nanocomposites with Fe3O4 magnetic core and CdSe/ZnS quantum dots shell.

This paper describes a new method for self-assembling multifunctional nanocomposites with a magnetic core of iron oxide Fe(3)O(4) and a shell of CdSe/ZnS quantum dots (QDs). Two sol-gel processes were applied to form the uniform magnetic seeds (Fe(3)O(4)@SiO(2)-SH) and then the thiol coordination was used to bind the CdSe/ZnS QDs to the surface of the seeds. The multifunctional nanocomposites were characterized by means of transmission electron microscopy, X-ray diffraction, energy disperse spectroscopy, fluorescence spectroscopy, infrared spectroscopy, and superconducting quantum interference device (SQUID) magnetometer. The results showed that the magnetic Fe(3)O(4) nanoparticles and the CdSe/ZnS fluorescent QDs were combined together. The nanocomposites were of spherical shape with a mean diameter of 25 nm and exhibited well magnetic response, photostability, chemical activity, and water miscibility. The method put forward here can also be extended to combine systems of other metal oxides and QDs to fabricate core-shell nanocomposites with multifunction for biomedical applications.

Expression and immunogenicity of Mycoplasma hyopneumoniae heat shock protein antigen P42 by DNA vaccination.

Mycoplasma hyopneumoniae is the etiological agent of swine enzootic pneumonia, a chronic nonfatal disease affecting pigs of all ages. The goal of this study was to design DNA vaccines by constructing plasmid pcDNA3/P42, carrying the heat shock protein gene P42 of M. hyopneumoniae, and to evaluate the immune responses elicited in BALB/c mice. The expression of P42 was first examined in transfected NIH 3T3 cells by reverse transcription-PCR to ensure that the construct was functional. The humoral and cell-mediated immune responses induced by the plasmid were further evaluated in BALB/c mice through intramuscular injection. Both immunoglobulin G1 (IgG1) and IgG2a levels were 64 times those of the control groups during the first 8 weeks. The levels of interleukin-2 (IL-2), IL-4, and gamma interferon mRNAs in the immunized animals were elevated, and the proliferation of spleen cells was also enhanced in the immunized animals. The results indicate that pcDNA3/P42 DNA immunization induces both Th1 and Th2 immune responses. In addition, antiserum from the immunized animals was found to inhibit the growth of M. hyopneumoniae. The present study reveals that DNA vaccination could be a new strategy against infection by M. hyopneumoniae and may have potential for developing vaccines for other infectious diseases as well.