Bawa R.,Bawa Biotechnology Consulting LLC |
Bawa R.,Rensselaer Polytechnic Institute |
Bawa R.,Synergene Therapeutics Inc
European Journal of Nanomedicine | Year: 2010
There is enormous excitement and expectation surrounding the multidisciplinary field of nanotechnology. This carries over to nanomedicine - the application of nanotechnology to healthcare - which is already influencing the pharmaceutical industry, especially in the design, formulation and delivery of therapeutics. Nanopharmaceuticals are a relatively new class of therapeutic-containing nanomaterials that often have unique " nanoproperties" (physiochemical properties) due to their small size (compared with their bulk-phase counterparts) a high surface-to-volume ratio and the possibility of modulating their properties. Basically they are nanoparticles intended for a broad spectrum of clinical therapeutic applications with the potential to target a particular organ or tissue site, either passively or actively. Nanopharmaceuticals present novel reformulation opportunities for active agents (e.g., single molecule drugs, proteins, nucleic acids, etc.) that were previously insoluble or could not be targeted to a specific site of the body where they were needed. In other words, those therapeutic agents that were previously unsuitable for traditional oral or injectable drug formulations could now be "nanoformulated" for delivery to specific biological targets due to superior pharmacokinetics/ pharmacodynamics and/or active intracellular delivery. As a result, this approach has the ability to reduce toxicity and enhance bioavailability, thereby improving efficacy and patient compliance. Nanopharmaceuticals can also increase drug half-life by reducing immunogenicity and diminishing drug metabolism. With these advantages, nanopharmaceuticals have the ability to extend the economic life of proprietary drugs, thereby creating additional revenue streams. As a result, they have the potential to impact drug commercialization and the healthcare landscape. Inevitably they will become an integral part of mainstream medicine. A large number of the US Food and Drug Administration (FDA)-approved nanopharmaceuticals have already been launched while many more are in various phases of clinical trials.
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 201.74K | Year: 2004
DESCRIPTION (provided by applicant): In this application, the long-term goal is the development of an effective tumor-targeting lipoplex for systemic treatment of pancreatic cancer (PanCa), which has one of the worst prognosis of all human malignancies. Our previous studies indicate that cancer cells can be sensitized to radiation/chemotherapy via p53 restoration ,using a tumor-targeting liposomal gene delivery system. For the delivery of the wtp53 gene, as well as other genes, we have developed a ligand, tumor-targeting liposome complex, a nanoparticle delivery system (NDS). This resulted not only in tumor growth inhibition and/or increased survival, but also, in complete, long-term elimination of some tumors in mouse models of cancer when combined with either radiation or chemotherapy. To further achieve improvement in transfection efficiency of our NDS, recently we have designed the inclusion of a pH sensitive cationic HK peptide (histidylated oligolysine) in the complex to enhance DNA release from the endosome. One of the advantages of our NDS is that it can be broadly employed for numerous tumor types. Thus, in this application we will focus on PanCa. The major aims of this STTR I proposal are to optimize this modified complex and evaluate its transfection efficiency in vitro and its in vivo targeting ability for PanCa tumors. The assessment of this novel NDS with respect to its potential for efficient tumor-targeting delivery and antitumor efficacy can be cumbersome when based solely on biological assays, particularly in regards to product release criteria for production of therapeutic agents. Consequently, the development of methods for characterizing NDS using physical parameters would be essential. Joining forces with Dr. John Dagata at NIST, we propose to use advanced imaging analysis including atomic force microscopy, electric force microscopy, and phase imaging to characterize the NDS and correlate the results of these physical analyses with the observed biological effects of the complex. This will allow us to leverage our efforts in a pioneering attempt to bridge the gap between two distinct technologies, thus developing new engineering methodologies to characterize, design and improve therapeutic delivery systems. In addition, establishing new technologies to assess the physical characteristics of NDS will also aid in developing more precise product release criteria for these biological therapeutics.
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 478.86K | Year: 2006
DESCRIPTION (provided by applicant): The low rate of cure of pancreatic carcinoma is an important health problem. The American Cancer Society estimates that 32,000 Americans will be diagnosed with carcinoma of the pancreas in 2005, and 31,800 will die. Pancreatic cancer is the fourth leading cause of cancer death in the US. Early detection appears currently to be the only way of improving the high mortality rate, but is quite difficult because of the retroperitoneal location of the pancreas and the lack of symptoms in early disease. We are proposing to further develop a MR tumor targeting imaging agent with a high affinity for entering carcinoma cells. Current imaging methods for the pancreas include ultrasound, CT, MRI, and PET. Each of these is moderately to very good for imaging the pancreas and for staging pancreatic neoplasm, but each relies on indirect signs of carcinoma based on the identification of a mass, lesion vascularity, or its glucose utilization. These features are also present in the main mimicker of pancreatic carcinoma; benign masses from chronic pancreatitis. Anti-transferrin Receptor scFv-antibody fragment (TfRscFv) immunoliposome complex is a nano-construct (
Kim S.-S.,Georgetown University |
Harford J.B.,Synergene Therapeutics Inc |
Pirollo K.F.,Georgetown University |
Chang E.H.,Georgetown University
Biochemical and Biophysical Research Communications | Year: 2015
Glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain tumor. Both therapeutic resistance and restricted permeation of drugs across the blood-brain barrier (BBB) play a major role in the poor prognosis of GBM patients. Accumulated evidence suggests that in many human cancers, including GBM, therapeutic resistance can be attributed to a small fraction of cancer cells known as cancer stem cells (CSCs). CSCs have been shown to have stem cell-like properties that enable them to evade traditional cytotoxic therapies, and so new CSC-directed anti-cancer therapies are needed. Nanoparticles have been designed to selectively deliver payloads to relevant target cells in the body, and there is considerable interest in the use of nanoparticles for CSC-directed anti-cancer therapies. Recent advances in the field of nanomedicine offer new possibilities for overcoming CSC-mediated therapeutic resistance and thus significantly improving management of GBM. In this review, we will examine the current nanomedicine approaches for targeting CSCs and their therapeutic implications. The inhibitory effect of various nanoparticle-based drug delivery system towards CSCs in GBM tumors is the primary focus of this review. © 2015 Elsevier Inc. All rights reserved.
Senzer N.,Mary Crowley Cancer Research Centers |
Nemunaitis J.,Mary Crowley Cancer Research Centers |
Nemunaitis D.,Mary Crowley Cancer Research Centers |
Bedell C.,Mary Crowley Cancer Research Centers |
And 7 more authors.
Molecular Therapy | Year: 2013
Selective delivery of therapeutic molecules to primary and metastatic tumors is optimal for effective cancer therapy. A liposomal nanodelivery complex (scL) for systemic, tumor-targeting delivery of anticancer therapeutics has been developed. scL employs an anti-transferrin receptor (TfR), scFv as the targeting molecule. Loss of p53 suppressor function, through mutations or inactivation of the p53 pathway, is present in most human cancers. Rather than being transiently permissive for tumor initiation, persistence of p53 dysfunction is a continuing requirement for maintaining tumor growth. Herein, we report results of a first-in-man Phase I clinical trial of restoration of the normal human tumor suppressor gene p53 using the scL nanocomplex (SGT-53). Minimal side effects were observed in this trial in patients with advanced solid tumors. Furthermore, the majority of patients demonstrated stable disease. One patient with adenoid cystic carcinoma had his status changed from unresectable to resectable after one treatment cycle. More significantly, we observed an accumulation of the transgene in metastatic tumors, but not in normal skin tissue, in a dose-related manner. These results show not only that systemically delivered SGT-53 is well tolerated and exhibits anticancer activity, but also supply evidence of targeted tumor delivery of SGT-53 to metastatic lesions. © The American Society of Gene & Cell Therapy.