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Articles 1 - 9 of 9
Full-Text Articles in Pharmacy and Pharmaceutical Sciences
Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari
Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari
Pharmacy Faculty Articles and Research
A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)5C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl3 with [(WR)5C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm. Flow cytometry investigation showed that the cellular uptake of a cell-impermeable fluorescence-labeled phosphopeptide (F′-GpYEEI, where F′ = fluorescein) was approximately six times higher in the presence of [(WR) …
Investigation Of Enzymatically Synthesized Glycogen As A Novel Nanodendrimer For Therapeutic Delivery, Sarah Ann Engelberth
Investigation Of Enzymatically Synthesized Glycogen As A Novel Nanodendrimer For Therapeutic Delivery, Sarah Ann Engelberth
Legacy Theses & Dissertations (2009 - 2024)
The field of medicinal chemistry is ever expanding, designing and discovering new therapeutic strategies. Oftentimes, it is challenging for these therapeutics to undergo clinical translation due to ineffective administration or unwanted toxicity in vivo. As such, drug delivery vehicles are designed to overcome these hurdles, allowing for delivery to the site of action by improving biodistribution, protecting therapeutic cargo, and decreasing toxicity. The work presented here aims to investigate a naturally-derived carbohydrate nanodendrimer, enzymatically synthesized glycogen (ESG) for drug delivery. This nontoxic, highly-branched, glucose-based structure has interior void volumes to allow for cargo encapsulation as well as a large density …
Doxorubicin Loaded Polymeric Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun K. Iyer, Keinosuke Ryu, Francis John Hornicek, Henry J. Mankin, Mansoor M. Amiji, Zhenfeng Duan
Doxorubicin Loaded Polymeric Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun K. Iyer, Keinosuke Ryu, Francis John Hornicek, Henry J. Mankin, Mansoor M. Amiji, Zhenfeng Duan
Arun Iyer
Background: Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the …
Inhibition Of Abcb1 (Mdr1) Expression By An Sirna Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun Iyer, Keinosuke Ryu, Edwin Choi, Francis Hornicek, Henry Mankin, Lara Milane, Mansoor Amiji, Zhenfeng Duan
Inhibition Of Abcb1 (Mdr1) Expression By An Sirna Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun Iyer, Keinosuke Ryu, Edwin Choi, Francis Hornicek, Henry Mankin, Lara Milane, Mansoor Amiji, Zhenfeng Duan
Arun Iyer
Background: The use of neo-adjuvant chemotherapy in treating osteosarcoma has improved patients’ average 5 year survival rate from 20% to 70% in the past 30 years. However, for patients who progress after chemotherapy, its effectiveness diminishes due to the emergence of multi-drug resistance (MDR) after prolonged therapy. Methodology/Principal Findings: In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure resulting from MDR, we designed and evaluated a novel drug delivery system for MDR1 siRNA delivery. Novel biocompatible, lipid-modified dextran-based polymeric nanoparticles were used as the platform for MDR1 siRNA delivery; and the efficacy …
Fluorescence-Guided Optical Coherence Tomography Imaging For Colon Cancer Screening: A Preliminary Mouse Study., Arun K. Iyer
Fluorescence-Guided Optical Coherence Tomography Imaging For Colon Cancer Screening: A Preliminary Mouse Study., Arun K. Iyer
Arun Iyer
A new concept for cancer screening has been preliminarily investigated. A cancer targeting agent loaded with a near-infrared (NIR) dye was topically applied on the tissue to highlight cancer-suspect locations and guide optical coherence tomography (OCT) imaging, which was used to further investigate tissue morphology at the micron scale. A pilot study on ApcMin mice has been performed to preliminarily test this new cancer screening approach. As a cancer-targeting agent, poly(epsilon-caprolactone) microparticles (PCLMPs), labeled with a NIR dye and functionalized with an RGD (argenine-glycine-aspartic acid) peptide, were used. This agent recognizes the α(ν)β(3) integrin receptor (ABIR), which is over-expressed by …
Combinatorial-Designed Multifunctional Polymeric Nanosystems For Tumor-Targeted Therapeutic Delivery., Arun K. Iyer
Combinatorial-Designed Multifunctional Polymeric Nanosystems For Tumor-Targeted Therapeutic Delivery., Arun K. Iyer
Arun Iyer
By definition, multifunctional nanosystems include several features within a single construct so that these devices can target tumors or other disease tissue, facilitate in vivo imaging, and deliver a therapeutic agent. Investigations of these nanosystems are rapidly progressing and provide new opportunities in the management of cancer. Tumor-targeted nanosystems are currently designed based primarily on the intrinsic physico-chemical properties of off-the-shelf polymers. Following fabrication, the surfaces of these nanoscale structures are functionalized for passive or active targeted delivery to the tumors. In this Account, we describe a novel approach for the construction of multifunctional polymeric nanosystems based on combinatorial design …
Oxystress Inducing Antitumor Therapeutics Via Tumor-Targeted Delivery Of Peg-Conjugated D-Amino Acid Oxidase., Arun Iyer
Arun Iyer
We had developed a H(2)O(2) generating enzyme, polyethylene glycol conjugated D-amino acid oxidase (PEG-DAO), which exhibited potent antitumor activity by generating toxic reactive oxygen species, namely oxidation therapy, subsequently showed remarkable antitumor effect on murine Sarcoma 180 solid tumor, by taking advantage of the enhanced permeability and retention effect. Along this line, we report here the preparation of PEG-DAO by use of recombinant DAO and its antitumor activity by using various tumor cell lines and tumor models. Recombinant DAO (rDAO) was obtained from E. coli BL21 (DE3) carrying the porcine DAO expression vector with high yield (20 mg/l) and high …
High-Loading Nanosized Micelles Of Copoly(Styrene-Maleic Acid)-Zinc Protoporphyrin For Targeted Delivery Of A Potent Heme Oxygenase Inhibitor., Arun Iyer
Arun Iyer
Amphiphilic styrene-maleic acid (SMA) copolymer efficiently formed micelles with a potent heme oxygenase inhibitor-zinc protoporphyrin (ZnPP). The micelles were constructed by subtle pH adjustments to form non-covalent interaction between the hydrophobic ZnPP and amphiphilic SMA. The micelles (SMA-ZnPP) thus formed were nanoparticles with narrow size distribution in water (mean diameter 176.5nm), having tunable loading (from 15% to 60% w/w of ZnPP) with remarkable aqueous solubility. SMA-ZnPP had an average molecular size of 144kDa as determined by size-exclusion chromatography (SEC), this size is a marked increase from the molecular weight of free ZnPP (626.03Da), suggesting the formation of micellar structure. The …
Exploiting The Enhanced Permeability And Retention Effect For Tumor Targeting., Arun Iyer
Exploiting The Enhanced Permeability And Retention Effect For Tumor Targeting., Arun Iyer
Arun Iyer
Of the tumor targeting strategies, the enhanced permeability and retention (EPR) effect of macromolecules is a key mechanism for solid tumor targeting, and considered a gold standard for novel drug design. In this review, we discuss various endogenous factors that can positively impact the EPR effect in tumor tissues. Further, we discuss ways to augment the EPR effect by use of exogenous agents, as well as practical methods available in the clinical setting. Some innovative examples developed by researchers to combat cancer by the EPR mechanism are also discussed.