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Lincoln, NE, United States

Mezzaroba N.,University of Trieste | Zorzet S.,University of Trieste | Secco E.,University of Trieste | Biffi S.,Institute for Maternal and Child Health IRCCS Burlo Garofolo | And 18 more authors.
PLoS ONE | Year: 2013

Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders. © 2013 Mezzaroba et al. Source

Marin G.H.,CUCAIBA | Mansilla E.,CUCAIBA | Mezzaroba N.,University of Trieste | Zorzet S.,University of Trieste | And 12 more authors.
Current Clinical Pharmacology | Year: 2010

The aim of this study was to determine if Rituximab coated Biodegradable Nanoparticles (BNPs) loaded with Chlorambucil and Hydroxychloroquine could induce apoptosis of B-Chronic Lymphocytic Leukemia (B-CLL), MEC-1 and BJAB cells in vitro and evaluate their toxic and therapeutic effects on a Human/Mouse Model of Burkitt Lymphoma at an exploratory, proof of concept scale. We found that Rituximab-Chlorambucil-Hydroxychloroquine BNPs induce a decrease in cell viability of malignant B cells in a dose-dependent manner. The mediated cytotoxicity resulted from apoptosis, and was confirmed by monitoring the B-CLL cells after Annexin V/propidium iodide staining. Additional data revealed that these BNPs were non toxic for healthy animals, and had prolonged survival in this mice model of human lymphoma. © 2010 Bentham Science Publishers Ltd. Source

Capolla S.,University of Trieste | Garrovo C.,Institute for Maternal and Child Health IRCCS Burlo Garofolo | Zorzet S.,University of Trieste | Lorenzon A.,Animal Care Unit | And 8 more authors.
International Journal of Nanomedicine | Year: 2015

The expectations of nanoparticle (NP)-based targeted drug delivery systems in cancer, when compared with convectional therapeutic methods, are greater efficacy and reduced drug side effects due to specific cellular-level interactions. However, there are conficting literature reports on enhanced tumor accumulation of targeted NPs, which is essential for translating their applications as improved drug-delivery systems and contrast agents in cancer imaging. In this study, we characterized biodegradable NPs conjugated with an anti-CD20 antibody for in vivo imaging and drug delivery onto tumor cells. NPs’ binding specificity mediated by anti-CD20 antibody was evaluated on MEC1 cells and chronic lymphocytic leukemia patients’ cells. The whole-body distribution of untargeted NPs and anti-CD20 NPs were compared by time-domain optical imaging in a localized human/mouse model of B-cell malignancy. These studies provided evidence that NPs’ functionalization by an anti-CD20 antibody improves tumor pharmacoki-netic profiles in vivo after systemic administration and increases in vivo imaging of tumor mass compared to non-targeted NPs. Together, drug delivery and imaging probe represents a promising theranostics tool for targeting B-cell malignancies. © 2015 Capolla et al. Source

Agency: Department of Defense | Branch: Office for Chemical and Biological Defense | Program: SBIR | Phase: Phase I | Award Amount: 70.00K | Year: 2010

In general, many biological and chemical agents affect the lungs directly or indirectly, even if the respiratory system is not the primary target organ of a military or terrorist attack. Both in the case of military and civilian attacks the lung can be one of the first organs affected by a chemical or biological agent. LNK Chemsolutions (LNK) with expertise in nanoparticle formulations and the University of Illinois Chicago with expertise in Acute Lung Injury (ALI) molecular biology and treatment modality development have teamed up to develop novel oral and inhalation formulation of targeted nanoparticles (NPs) containing siRNA and/or miRNA to improve the treatment of ALI unobtainable with current delivery systems.

LNK Chemsolutions, LLC | Date: 2012-03-08

A method of manufacturing a sturdy and pliable fibrous hemostatic dressing by making fibers that maximally expose surface area per unit weight of active ingredients as a means for aiding in the clot forming process and as a means of minimizing waste of active ingredients. The method uses a rotating object to spin off a liquid biocompatible fiber precursor, which is added at its center. Fibers formed then deposit on a collector located at a distance from the rotating object creating a fiber layer on the collector. An electrical potential difference is maintained between the rotating disk and the collector. Then, a liquid procoagulation species is introduced at the center of the rotating disk such that it spins off the rotating disk and coats the fibers.

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