Pharmacy and Pharmaceutical Sciences Commons^™

Encapsulation And Controlled Release Of Rhu-Erythropoietin From Chitosan Biopolymer Nanoparticles, Cody Bulmer

Electronic Thesis and Dissertation Repository

The objective of this research project was to develop a drug delivery system for recombinant human erythropoietin (rHu-EPO), a glycoprotein hormone used in the treatment of renal anaemia and chemotherapy induced anaemia, using the biopolymer chitosan as the base component. Two types of chitosan nanoparticles were produced through ionotropic gelation using flush mixing with either tripolyphosphate (TPP) or carrageenan polymer. Chitosan-TPP and chitosan-carrageenan nanoparticles were generated under a variety of conditions to evaluate the effects of chitosan concentration, chitosan to anion mass ratio and solution pH on the nanoparticle characteristics of particle diameter, surface charge and particle size distribution. A …

Ceria-Engineered Nanomaterial Distribution In, And Clearance From, Blood: Size Matters, Mo Dan, Peng Wu, Eric A. Grulke, Uschi M. Graham, Jason M. Unrine, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

AIMS: Characterize different sized ceria-engineered nanomaterial (ENM) distribution in, and clearance from, blood (compared to the cerium ion) following intravenous infusion.

MATERIALS & METHODS: Cerium (Ce) was quantified in whole blood, serum and clot (the formed elements) up to 720 h.

RESULTS: Traditional pharmacokinetic modeling showed best fit for 5 nm ceria ENM and the cerium ion. Ceria ENMs larger than 5 nm were rapidly cleared from blood. After initially declining, whole blood 15 and 30 nm ceria increased (results that have not been well-described by traditional pharmacokinetic modeling). The cerium ion and 5 and 55 nm ceria did not …

Gene Therapy In The Cornea: 2005--Present, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Ashish Tandon

Pharmacy Faculty Articles and Research

Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made in the field of corneal gene therapy in last 5 years. Several new gene transfer vectors, techniques and approaches have evolved. Although corneal gene therapy is still in its early stages of development, the potential of gene-based interventions to treat …

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 …

Nanoparticulate Formulations Of Mithramycin Analogs For Enhanced Cytotoxicity, Daniel Scott, Jürgen Rohr, Younsoo Bae

Pharmaceutical Sciences Faculty Publications

Mithramycin (MTM), a natural product of soil bacteria from the Streptomyces genus, displays potent anticancer activity but has been limited clinically by severe side effects and toxicities. Engineering of the MTM biosynthetic pathway has produced the 3-side-chain-modified analogs MTM SK (SK) and MTM SDK (SDK), which have exhibited increased anticancer activity and improved therapeutic index. However, these analogs still suffer from low bioavailability, short plasma retention time, and low tumor accumulation. In an effort to aid with these shortcomings, two nanoparticulate formulations, poly(ethylene glycol)-poly(aspartate hydrazide) self-assembled and cross-linked micelles, were investigated with regard to the ability to load and pH …

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 …

Compositions Comprising Human Immunodeficiency Virus Tat Adsorbed To The Surface Of Anionic Nanoparticles, Russell J. Mumper, Jerold Woodward, Zhengrong Cui, Avindra Nath

Pharmaceutical Sciences Faculty Patents

Non-denatured, recombinant human immunodeficiency virus (HIV) Tat that is free of bacterial RNA and endotoxin is employed in an anti-HIV vaccine. A process of producing the recombinant Tat protein includes steps for removing bacterial RNA from the recombinant Tat and for removing endotoxin from the recombinant Tat protein. A Tat-adsorbed nanoparticle formulation and method of making the same. A method of vaccinating against and/or treating HIV infection comprises administering to a subject in need of such vaccination or treatment an immune-response inducing effective amount of the recombinant Tat protein.

Targeted Delivery Of Surface Modified Nanoparticles: Modulation Of Inflammation For Acute Lung Injury, Hari R. Desu

Theses and Dissertations (ETD)

The objective of the study is to demonstrate alleviation of pulmonary inflammation associated with acute lung injury (ALI) using novel surface modified nanoparticles. ALI is characterized by three main pathological events: I) pulmonary edema, II) excessive pro-inflammatory cytokines and chemokines production from alveolar epithelial and endothelial cells and III) leukocyte migration from blood circulation into alveoli. Currently, there is no FDA approved pharmacological treatment available except the supportive mechanical ventilation therapy. Numerous clinical trials involving pharmacological therapies aimed at different pathological targets turned unsuccessful. National Institute of Heart Lung and Blood Institute (NHLBI) cited underappreciation of drug delivery systems as …

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

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.