Nanomedicine Commons^™

Concepts Of Cancer And A Novel Cancer Therapy: Treating Tumors As An Aggressive Organ, Stephen J. Beebe

Bioelectrics Publications

No abstract provided.

Developent Of A Phospholipid Encapsulation Process For Quantum Dots To Be Used In Biologic Applications, Logan Grimes

Master's Theses

The American Cancer Society predicts that 1,665,540 people will be diagnosed with cancer, and 585,720 people will die from cancer in 2014. One of the most common types of cancer in the United States is skin cancer. Melanoma alone is predicted to account for 10,000 of the cancer related deaths in 2014. As a highly mobile and aggressive form of cancer, melanoma is difficult to fight once it has metastasized through the body. Early detection in such varieties of cancer is critical in improving survival rates in afflicted patients. Present methods of detection rely on visual examination of suspicious regions …

Nanotoxicity In Cells Of The Immune System, Jonathan J. Pelc

Science Scholars

Nanoparticles (NPs) provide a new medical approach to drug therapy. As with every new approach, safety precautions need to be taken, and the immediate and long-term effects for many NPs are still unclear. When administering a medical treatment into the human body, the first issue that needs to be addressed is host detection of the medicine and inflammation as a possible result of the treatment. If a new NP treatment causes inflammation before it releases its medicine, that treatment may be ineffective, even damaging to the patient. Small metallic and organic particles have been shown to elicit an inflammatory responses …

Targeting Breast Cancer With Bacteriophage Associated Silicon Particles, Srimeenakshi Srinivasan

Dissertations and Theses (Open Access)

Nanoparticle based therapeutics have been successfully used in the treatment of breast cancer. Development of nanovectors targeted to cancer cells or elements in the tumor microenvironment has been pursued to improve their site specific accumulation while reducing the non-specific delivery to normal tissues. However, addition of targeting ligands to the surface of nanovectors while maintaining their payload carrying potential is generally challenging. Therefore, there is a critical need to develop surface decoration strategies that allow for effective combination of targeting and payload delivery to the tumor.

In this study, we propose a novel strategy for covering the surface of mesoporous …

Bioactivity And Cell-Mediated Targeting Of Multistage Nanoporous Silicon Particles, Jonathan O. Martinez

Dissertations and Theses (Open Access)

Progress in drug delivery approaches have not adequately translated into clinical advances in the diagnosis or treatment of inflammatory disorders (e.g., cancer). This disconnect is rooted in the inefficient delivery of imaging and therapeutic agents to the inflamed site upon systemic delivery. A multitude of biological barriers pose insurmountable obstacles limiting the ability of the agent to effectively reach and accumulate at the target site. Nanoparticles (NP) surfaced as potential vectors to encapsulate and deliver biological agents. However, even after surface decoration, NP have failed to evade biological barriers (i.e., MPS) and to accumulate at the tumor site at therapeutic …

Design And Optimization Of Plga-Based Diclofenac Loaded Nanoparticles, Dustin L. Cooper, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Drug based nanoparticle (NP) formulations have gained considerable attention over the past decade for their use in various drug formulations. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Nonsteroidal anti-inflammatory drugs such as diclofenac block cyclooxygenase expression and reduce prostaglandin synthesis, which can lead to several side effects such as gastrointestinal bleeding and renal insufficiency. The aim of this study was to formulate and characterize diclofenac entrapped poly(lactide-co-glycolide) (PLGA) based nanoparticles. Nanoparticles were formulated using an emulsion-diffusion-evaporation technique with varying concentrations of poly vinyl alcohol (PVA) (0.1, 0.25, 0.5, or …

Therapeutic Efficacy Of Cerium Oxide Nanoparticles Against Sepsis Induced Multi-Organ Dysfunction Syndrome In Sprague Dawley Rats, Nandini Durga Prasanna Kumar Manne

Theses, Dissertations and Capstones

Sepsis is a generalized term that signifies the presence of a pathogen in the blood stream to which the body responds by eliciting a systemic inflammatory response. Although sepsis is the leading cause of death in non-coronary intensive care units in United States, there are currently no FDA approved therapeutic drugs to treat this disorder. Cerium oxide nanoparticles (CeO₂) have been shown to exhibit anti-oxidant, anti-inflammatory, and anti-bacterial properties both in vitro and in vivo. Whether CeO₂ nanoparticles can be used for the treatment of sepsis is currently unclear.

To investigate whether CeO₂ nanoparticles can …

Self-Assembly Of Peptides To Nanostructures, Dindyal Mandal, Amir Nasrolahi Shirazi, Keykavous Parang

Pharmacy Faculty Articles and Research

The formation of well-ordered nanostructures through self-assembly of diverse organic and inorganic building blocks has drawn much attention owing to their potential applications in biology and chemistry. Among all organic building blocks, peptides are one of the most promising platforms due to their biocompatibility, chemical diversity, and resemblance with proteins. Inspired from the protein assembly in biological systems, various self-assembled peptide structures have been constructed using several amino acids and sequences. This review focuses on this emerging area, the recent advances in peptide self-assembly, and formation of different nanostructures, such as tubular, fibers, vesicles, spherical, and rod coil structures. While …

In Vitro Analysis Of Nanoparticulate Hydroxyapatite/Chitosan Composites As Potential Drug Delivery Platforms For The Sustained Release Of Antibiotics In The Treatment Of Osteomyelitis, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Nanoparticulate composites of hydroxyapatite (HAp) and chitosan were synthesized by ultrasound-assisted sequential precipitation and characterized for their microstructure at the atomic scale, surface charge, drug release properties, and combined antibacterial and osteogenic response. Crystallinity of HAp nanoparticles was reduced because of the interference of the surface layers of chitosan with the dissolution/reprecipitation-mediated recrystallization mechanism that conditions the transition from the as-precipitated amorphous calcium phosphate phase to the most thermodynamically stable one—HAp. Embedment of 5–10 nm sized, narrowly dispersed HAp nanoparticles within the polymeric matrix mitigated the burst release of the small molecule model drug, fluorescein, bound to HAp by physisorption, …

Simultaneous Bactericidal And Osteogenic Effect Of Nanoparticulate Calcium Phosphate Powders Loaded With Clindamycin On Osteoblasts Infected With Staphylococcus Aureus, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

S aureus internalized by bone cells and shielded from the immune system provides a reservoir of bacteria in recurring osteomyelitis. Its targeting by the antibiotic therapy may thus be more relevant for treating chronic bone infection than eliminating only the pathogens colonizing the bone matrix. Assessed was the combined osteogenic and antibacterial effect of clindamycinloaded calcium phosphate nanoparticles of different monophasic compositions on co-cultures comprising osteoblasts infected with S aureus. Antibiotic-carrying particles were internalized by osteoblasts and minimized the concentration of intracellular bacteria. In vitro treatments of the infected cells, however, could not prevent cell necrosis due to the …

Nanoparticulate Drug Delivery Platforms For Advancing Bone Infection Therapies, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Introduction—The ongoing surge of resistance of bacterial pathogens to antibiotic therapies and the consistently aging median member of the human race signal an impending increase in the incidence of chronic bone infection. Nanotechnological platforms for local and sustained delivery of therapeutics hold the greatest potential for providing minimally invasive and maximally regenerative therapies for this rare but persistent condition.

Areas covered—Shortcomings of the clinically available treatment options, including poly(methyl methacrylate) beads and calcium sulfate cements, are discussed and their transcending using calcium-phosphate/polymeric nanoparticulate composites is foreseen. Bone is a composite wherein the weakness of each component alone is …

Modified Seed Growth Of Iron Oxide Nanoparticles In Benzyl Alcohol: Magnetic Nanoparticles For Radio Frequency Hyperthermia Treatment Of Cancer, Stanley E. Gilliland Iii

Theses and Dissertations

Iron oxide nanoparticles have received sustained interest for biomedical applications as synthetic approaches are continually developed for precise control of nanoparticle properties. This thesis presents an investigation of parameters in the benzyl alcohol synthesis of iron oxide nanoparticles. A modified seed growth method was designed for obtaining optimal nanoparticle properties for magnetic fluid hyperthermia. With a one or two addition process, iron oxide nanoparticles were produced with crystallite sizes ranging from 5-20 nm using only benzyl alcohol and iron precursor. The effects of reaction environment, temperature, concentration, and modified seed growth parameters were investigated to obtain precise control over properties …

Hybrid Nanostructured Textile Bioelectrode For Unobtrusive Health Monitoring, Pratyush Rai

Graduate Theses and Dissertations

Coronary heart disease, cardiovascular diseases and strokes are the leading causes of mortality in United States of America. Timely point-of-care health diagnostics and therapeutics for person suffering from these diseases can save thousands of lives. However, lack of accessible minimally intrusive health monitoring systems makes timely diagnosis difficult and sometimes impossible. To remedy this problem, a textile based nano-bio-sensor was developed and evaluated in this research. The sensor was made of novel array of vertically standing nanostructures that are conductive nano-fibers projecting from a conductive fabric. These sensor electrodes were tested for the quality of electrical contact that they made …

Combination Of Sirna-Directed Gene Silencing With Cisplatin Reverses Drug Resistance In Human Non-Small Cell Lung Cancer, Shanthi Ganesh, Arun K. Iyer, Jan Weller, David V. Morrissey, Mansoor M. Amiji

Pharmaceutical Sciences Faculty Publications

One of the most challenging aspects of lung cancer therapy is the rapid acquisition of multidrug-resistant (MDR) phenotype. One effective approach would be to identify and downregulate resistance-causing genes in tumors using small interfering RNAs (siRNAs) to increase the sensitivity of tumor cells to chemotherapeutic challenge. After identifying the overexpressed resistance-related antiapoptotic genes (survivin and bcl-2) in cisplatin-resistant cells, the siRNA sequences were designed and screened to select the most efficacious candidates. Modifications were introduced in them to minimize off-target effects. Subsequently, the combination of siRNA and cisplatin that gave the maximum synergy was identified in resistant cells. We then …

Design And Fabrication Of Nanofluidic Systems With Integrated Sensing Electrodes For Rapid Biomolecule Characterization, Taylor Bradley Busch

Graduate Theses and Dissertations

A transparent nanofluidic system with embedded sensing electrodes was designed and fabricated by integrating Atomic Force Microscopy (AFM) nanolithography, Focused Ion Beam (FIB) milling and metal deposition, and standard microfabrication processing. The fabrication process started with the evaporation of chrome/gold (Cr/Au) onto a Pyrex 7740 wafer followed by photolithography and wet etching of the microchannels. The wafer was patterned a second time to form Au microelectrodes with 15-45 micrometer separation gaps in the nanochannel region. Sensing electrodes (up to one micron wide) were then deposited using FIB to bridge the gaps. The nanochannels were realized through both AFM nanolithography and …

Phase Composition Control Of Calcium Phosphate Nanoparticles For Tunable Drug Delivery Kinetics And Treatment Of Osteomyelitis. Part 2: Antibacterial And Osteoblastic Response, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Osteomyelitis has been traditionally treated by the combination of long-term antibiotic therapies and surgical removal of diseased tissue. The multifunctional material was developed in this study with the aim to improve this therapeutic approach by: (a) enabling locally delivered and sustained release of antibiotics at a tunable rate, so as to eliminate the need for repetitive administration of systemically distributed antibiotics; and (b) controllably dissolving itself, so as to promote natural remineralization of the portion of bone lost to disease. We report hereby on the effect of the previously synthesized calcium phosphates (CAPs) with tunable solubilities and drug release time …

Calcium Phosphate Nanoparticles: A Future Therapeutic Platform For The Treatment Of Osteomyelitis?, Tejal A. Dasai, Vuk Uskoković

Pharmacy Faculty Articles and Research

No abstract provided.

Self-Assembled Surfactant Cyclic Peptide Nanostructures As Stabilizing Agents, Dindyal Mandal, Rakesh Tiwari, Amir Nasrolahi Shirazi, Donghoon Oh, Guofeng Ye, Antara Banerjee, Arpita Yadav, Keykavous Parang

Pharmacy Faculty Articles and Research

A number of cyclic peptides including [FR](4), [FK](4), [WK](5), [CR](4), [AK](4), and [WR](n) (n = 3-5) containing L-amino acids were produced using solid-phase peptide synthesis. We hypothesized that an optimal balance of hydrophobicity and charge could generate self-assembled nanostructures in aqueous solution by intramolecular and/or intermolecular interactions. Among all the designed peptides, [WR](n) (n = 3-5) generated self-assembled vesicle-like nanostructures at room temperature as shown by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and/or dynamic light scattering (DLS). This class of peptides represents the first report of surfactant-like cyclic peptides that self-assemble into nanostructures. A plausible mechanistic insight into …

Bmp7 Gene Transfer Via Gold Nanoparticles Into Stroma Inhibits Corneal Fibrosis In Vivo, Ashish Tandon, Ajay Sharma, Jason T. Rodier, Alexander M. Klibanov, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study examined the effects of BMP7 gene transfer on corneal wound healing and fibrosis inhibition in vivo using a rabbit model. Corneal haze in rabbits was produced with the excimer laser performing -9 diopters photorefractive keratectomy. BMP7 gene was introduced into rabbit keratocytes by polyethylimine-conjugated gold nanoparticles (PEI2- GNPs) transfection solution single 5-minute topical application on the eye. Corneal haze and ocular health in live animals was gauged with stereo- and slit-lamp biomicroscopy. The levels of fibrosis [a-smooth muscle actin (aSMA), F-actin and fibronectin], immune reaction (CD11b and F4/80), keratocyte apoptosis (TUNEL), calcification (alizarin red, vonKossa and osteocalcin), and …

Nanosecond Pulsed Electric Field (Nspef) Ablation As An Alternative Or Adjunct To Surgery For Treatment Of Cancer, Ru Chen, Xinhua Chen, Stephen J. Beebe

Bioelectrics Publications

Surgery as resection or transplantation remains a fundamental means for cancer treatment and often offers an opportunity for a cure. However, surgery is not always possible because of tumor proximity to blood vessels or ducts or when a patient is not healthy enough to undergo surgery. Application of nanosecond pulsed electric fields (nsPEFs) is a new approach to treat cancer using pulse power technology that was originally designed for military purposes. This novel approach deposits extremely short pulses of high power, low energy electric fields into malignant tissues using electrodes to encompass tumors. Pre-clinical studies show that treatments are effective …

Osteogenic And Antimicrobial Nanoparticulate Calcium Phosphate And Poly-(D, L-Lactide-Co-Glycolide) Powders For The Treatment Of Osteomyelitis, Vuk Uskoković, Charles Hoover, Marija Vukomanović, Dragan P. Uskoković, Tejal A. Dasai, Charles Hoover, Marija Vukomanović, Dragan P. Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Development of a material for simultaneous sustained and localized delivery of antibiotics and induction of spontaneous regeneration of hard tissues affected by osteomyelitis stands for an important clinical need. In this work, a comparative analysis of the bacterial and osteoblastic cell response to two different nanoparticulate carriers of clindamycin, an antibiotic commonly prescribed in the treatment of bone infection, one composed of calcium phosphate and the other comprising poly-(D,L-lactide-co-glycolide)-coated calcium phosphate, was carried out. Three different non-cytotoxic phases of calcium phosphate, exhibiting dissolution and drug release profiles in the range of one week to two months to one year, respectively, …

Nanoparticles Of Cobalt-Substituted Hydroxyapatite In Regeneration Of Mandibular Osteoporotic Bones, Nenad Ignjatović, Zorica Ajduković, Vojin Savić, Stevo Najman, Dragan Mihailović, Perica Vasilijević, Zoran Stojanović, Vuk Uskoković, Dragab Uskoković

Pharmacy Faculty Articles and Research

Indications exist that paramagnetic calcium phosphates may be able to promote regeneration of bone faster than their regular, diamagnetic counterparts. In this study, analyzed was the influence of paramagnetic cobalt-substituted hydroxyapatite nanoparticles on osteoporotic alveolar bone regeneration in rats. Simultaneously, biocompatibility of the material was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. The material was shown to be biocompatible and nontoxic when added to epithelial monolayers in vitro, while it caused a substantial decrease in the cell viability as well as deformation of the cytoskeleton and cell morphology when incubated with the osteoblastic …

Characterization Of Polymeric Phthalocyanine Nanoparticles Using Dynamic Light Scattering Laser, Satish Kumar Murarishetty

All Capstone Projects

The objective of this study is to use DLS (Dynamic Light Scattering) to analyze polymeric copper phthalocyanine nanoparticles (CuPcNPs). CuPcNPs are synthesized in order to facilitate drug penetration of bacterial biofilms for the treatment of chronic wounds. Microorganisms that reside inside the biofilms of chronic wounds are very resistant to any kind of treatment, even to the host’s own immune system. Therefore we have proposed an alternative method to destroy the microorganisms existing within the biofilms. Photodynamic anti-bacterial chemotherapy (PACT) has received much attention for the past decade due to the multi-drug resistant strands. PACT uses photons, a photosensitizer, and …

Nano Encapsulated Drug Delivery For Biofilms, Arunakanth Chavala

All Capstone Projects

Biofilms are now considered ubiquitous in the natural world. Bacterial biofilms have been observed to be extremely heterogeneous, both structurally and with regard to the physiology of the bacterial cells within them. The prevailing conceptual model depicts bacterial biofilms as being made up of microcolonies, which serve as the basic unit of the greater biofilm structure. A major concern with this approach is the frequently observed development of resistance to antimicrobial compounds. A number of elements in the process of biofilm formation have been studied as targets for novel drug delivery technologies. The present study aimed to penetrate biofilm by …

Nanoparticlated Drug Delivery System For Vitreous Humor, Kartheek K. Suragoni

All Capstone Projects

The purpose of this study is to develop a unique nanoparticulated system that has the capability of providing sustained drug delivery into the eyes. In ophthalmic preparations, poor ocular drug delivery of ocular dosage form is due to the production of tears and impermeability through corneal epithelium. The usage of liposomes in ophthalmic disorders shows promising results in ocular drug delivery. Liposomes are bilayered, microscopic vesicles surrounded by the aqueous compartments. Liposomes have the ability to encapsulate both hydrophilic and hydrophobic drugs. This unique property of liposomes helps in delivering the drug at specific site. This invention involves three major …

Using Photoactive Nanoparticles As Photodynamic Antimicrobial Chemotherapeutic (Pact) Agent To Treat Chronic Wounds, Chaitanya Poola

All Capstone Projects

The purpose of this study is to use photoactive vitamin nanoparticles as photodynamic antimicrobial chemotherapeutic agent to treat patients with chronic wounds. Chronic wounds are considered as a pandemic health problem which affects millions of people and increases ~10 % annually. According to the American Academy of Dermatology, the expense of treating chronic wounds constitutes over half of the total cost for all skin diseases. The main cause of chronic wounds is due to the existence of biofilms. Biofilms are complex microbial communities containing and are reported to be major factor contributing to multiple chronic inflammatory diseases. Owing to bacterial …

Bsa Nanoparticles For Sirna Delivery: Coating Effects On Nanoparticle Properties, Plasma Protein Adsorption, And In Vitro Sirna Delivery, Haran Yogasundaram, Markian Stephan Bahniuk, Harsh-Deep Singh, Hamidreza Montazeri Aliabadi, Hasan Uludag, Larry David Unsworth

Pharmacy Faculty Articles and Research

Developing vehicles for the delivery of therapeutic molecules, like siRNA, is an area of active research. Nanoparticles composed of bovine serum albumin, stabilized via the adsorption of poly-L-lysine (PLL), have been shown to be potentially inert drug-delivery vehicles. With the primary goal of reducing nonspecific protein adsorption, the effect of using comb-type structures of poly(ethylene glycol) (1 kDa, PEG) units conjugated to PLL (4.2 and 24 kDa) on BSA-NP properties, apparent siRNA release rate, cell viability, and cell uptake were evaluated. PEGylated PLL coatings resulted in NPs with ζ-potentials close to neutral. Incubation with platelet-poor plasma showed the composition of …

Attenuation Of Corneal Myofibroblast Development Through Nanoparticle-Mediated Soluble Transforming Growth Factor-Β Type Ii Receptor (Stgfβrii) Gene Transfer, Ajay Sharma, Jason T. Rodier, Ashish Tandon, Alexander M. Klibanov, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: To explore (i) the potential of polyethylenimine (PEI)-DNA nanoparticles as a vector for delivering genes into human corneal fibroblasts, and (ii) whether the nanoparticle-mediated soluble extracellular domain of the transforming growth factor–β type II receptor (sTGFβRII) gene therapy could be used to reduce myofibroblasts and fibrosis in the cornea using an in vitro model.

Methods: PEI-DNA nanoparticles were prepared at a nitrogen-to-phosphate ratio of 30 by mixing linear PEI and a plasmid encoding sTGFβRII conjugated to the fragment crystallizable (Fc) portion of human immunoglobulin. The PEI-DNA polyplex formation was confirmed through gel retardation assay. Human corneal fibroblasts (HCFs) were …

Detection Of Folate Binding Protein, Anwer Unnisa

All Capstone Projects

Cancer is the second leading cause of death despite the anti cancer developments including hormone therapy, radiotherapy, chemotherapy. Chemotherapy includes use of potent drugs such as camptothecin, paclitaxel and mitomycin. These drugs have an effect which is dose responsive, where the drug exposure and cell kill are proportional. This chemotherapy is high dose and has less selectivity for cancer cells and has more toxic effect to normal cells. Such kind of non specific treatment to tumor is causing hurdles in the treatment of cancer by chemotherapy. To overcome this current limitation to chemotherapy, the anti cancer drug with high specificity …

Using Photoactive Vitamin Nanoparticles As Photodynamic Antimicrobial Chemotherapeutic (Pact) Agents To Treat Chronic Wounds, Rahul A. Khanke

All Capstone Projects

The objective of the proposed study is to develop new materials and methods to manage microbial growth in chronic wounds using phototherapy. Chronic wounds are considered as a worldwide health problem. The most common chronic wounds can be classified into three categories: venous ulcers, diabetic ulcers, and pressure ulcers. Venous ulcers, which usually occur in the legs, account for about 70% to 90% of chronic wounds and can become infected easily. Venous ulcers are sores that develop after veins in the legs have been damaged. These ulcers can penetrate deeply into the skin. Occasionally, if a venous ulcer persists for …