3 H Dendrimer Nanoparticle Organ/Tumor Distribution

Purpose. To determine the in vivo biodistribution for differently charged poly(amidoamine) (PAMAM) dendrimers in B16 melanoma and DU145 human prostate cancer mouse tumor model systems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41504/1/11095_2004_Article_482250.pd

Understanding specific and nonspecific toxicities: a requirement for the development of dendrimer-based pharmaceuticals

Dendrimer conjugates for pharmaceutical development are capable of enhancing the local delivery of cytotoxic drugs. The ability to conjugate different targeting ligands to the dendrimer allows for the cytotoxic drug to be focused at the intended target cell while minimizing collateral damage in normal cells. Dendrimers offer several advantages over other polymer conjugates by creating a better defined, more monodisperse therapeutic scaffold. Toxicity from the dendrimer, targeted and nonspecific, is not only dependent upon the number of targeting and therapeutic ligands conjugated, but can be influenced by the repeating building blocks that grow the dendrimer, the dendrimer generation, as well as the surface termination. Copyright © 2010 John Wiley & Sons, Inc. For further resources related to this article, please visit the WIREs website .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69178/1/79_ftp.pd

Pre-Clinical Evaluation of a Novel Nanoemulsion-Based Hepatitis B Mucosal Vaccine

Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepatitis B vaccine composed of recombinant hepatitis B surface antigen (HBsAg) in a novel nanoemulsion (NE) adjuvant (HBsAg-NE) could be effective with fewer administrations.Physical characterization indicated that HBsAg-NE consists of uniform lipid droplets (349+/-17 nm) associated with HBsAg through electrostatic and hydrophobic interactions. Immunogenicity of HBsAg-NE vaccine was evaluated in mice, rats and guinea pigs. Animals immunized intranasally developed robust and sustained systemic IgG, mucosal IgA and strong antigen-specific cellular immune responses. Serum IgG reached > or = 10(6) titers and was comparable to intramuscular vaccination with alum-adjuvanted vaccine (HBsAg-Alu). Normalization showed that HBsAg-NE vaccination correlates with a protective immunity equivalent or greater than 1000 IU/ml. Th1 polarized immune response was indicated by IFN-gamma and TNF-alpha cytokine production and elevated levels of IgG(2) subclass of HBsAg-specific antibodies. The vaccine retains full immunogenicity for a year at 4 degrees C, 6 months at 25 degrees C and 6 weeks at 40 degrees C. Comprehensive pre-clinical toxicology evaluation demonstrated that HBsAg-NE vaccine is safe and well tolerated in multiple animal models.Our results suggest that needle-free nasal immunization with HBsAg-NE could be a safe and effective hepatitis B vaccine, or provide an alternative booster administration for the parenteral hepatitis B vaccines. This vaccine induces a Th1 associated cellular immunity and also may provide therapeutic benefit to patients with chronic hepatitis B infection who lack cellular immune responses to adequately control viral replication. Long-term stability of this vaccine formulation at elevated temperatures suggests a direct advantage in the field, since potential excursions from cold chain maintenance could be tolerated without a loss in therapeutic efficacy

Electronic-structure study of Ni<SUB>81</SUB>Cr<SUB>15</SUB>B<SUB>4</SUB> metallic glass using photoemission spectroscopy

X-ray- and ultraviolet-photoelectron spectroscopic studies of the core levels and the valence band of amorphous and crystalline (annealed at 800 K) Ni81Cr15B4 metallic glass are presented, and a comparison has been made of the valence-band spectra with those of the constituent elements. The single broad band appearing in the vicinity of the Fermi level in the spectrum of amorphous Ni81Cr15B4 is attributed to the d-band combination of both nickel and chromium. The low-lying states arise due to hybridization of metal-metalloid levels. The Ni3B phase has been detected in crystalline Ni81Cr15B4. The binding energy changes in the Ni 2p3/2, Cr 2p3/2, and B 1s levels, the variation of the Ni 2p3/2 satellite intensity, and asymmetry-index changes for the core lines have been used to support the above picture as well as to arrive at a comprehensive understanding of the density-of-states variation at the Fermi level. The charge-transfer mechanism between constituent elements in metallic glasses is also discussed

Surface oxidation study of Fe<SUB>67</SUB>Co<SUB>18</SUB>B<SUB>14</SUB>Si<SUB>1</SUB> metallic glass using Auger electron spectroscopy

Surface composition and depth profile of native oxide on Fe67Co18B14Si1 metallic glass has been investigated using Auger electron spectroscopy. The native oxide is compared with chemisorbed oxygen on the cleaned surface. Results indicate that boron segregates on the surface in the presence of oxygen. The low energy L23M45M45 peak of iron in metallic glass is compared with that in crystallized sample and pure iron foil