Nanotechnology Commons^™

Development Of Long-Acting Antiviral Drug Nanoformulations, Denise Cobb

Theses & Dissertations

Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, opportunities to improve its profile abound. ART is limited by putative viral reservoir penetrance, emergence of viral mutations, inherent toxicities, and regimen non-adherence. These highlight the need improved drug delivery schemes. Previously, our lab has demonstrated that targeting mononuclear phagocytes for antiretroviral drug delivery extends drug half-life and improves penetrance into viral reservoirs, addressing these limitations of ART. Herein, we developed synthetic and biologic antiretroviral (ARV) drug nanocarriers improve the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ARVs through …

Plga Nanoparticle-Based Formulations To Cross The Blood–Brain Barrier For Drug Delivery: From R&D To Cgmp, Kaining Zhi, Babatunde Raji, Anantha R. Nookala, Mohammad Moshahid Khan, Xuyen H. Nguyen, Swarna Sakshi, Tayebeh Pourmotabbed, Murali M. Yallapu

School of Medicine Publications

The blood–brain barrier (BBB) is a natural obstacle for drug delivery into the human brain, hindering treatment of central nervous system (CNS) disorders such as acute ischemic stroke, brain tumors, and human immunodeficiency virus (HIV)-1-associated neurocognitive disorders. Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible polymer that is used in Food and Drug Administration (FDA)-approved pharmaceutical products and medical devices. PLGA nanoparticles (NPs) have been reported to improve drug penetration across the BBB both in vitro and in vivo. Poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), and poloxamer (Pluronic) are widely used as excipients to further improve the stability and effectiveness of PLGA …

Remotely Controlled Enzyme Behavior Using Localized Thermal Gradients, Sarah Brown

UNO Student Research and Creative Activity Fair

No existing model describes an identified special case of enzyme behavior when directly stimulated with thermal energy via an RF field.

The ability to remotely influence cellular functions and outcomes is a new approach to targeted medicine. Nano-medicine and biotechnology are the future of medical diagnostics and treatment. The ability to remotely influence cellular functions and outcomes is a new approach to targeted medicine. Direct heating of an enzyme vs bulk heating changes the enzyme activity.

I tested how direct transfer of thermal energy changes rates of enzyme reactions. We created samples of enzymes, attached to ferrous (magnetic) nano-particles, and …

The Antioxidant And Antimicrobial Activities Of Cornsilk Extract Encapsulated In Polysaccharide Nanoparticles, Maryam Mady

Theses and Dissertations

Corn silk possess antibacterial and antioxidant activities due to its phenolic compounds but they are of low bioavailability that requires some innovative techniques to develop such active ingredients in a safe and less toxic manner. Accordingly, silk extract SE was encapsulated in chitosan nanoparticles CS NPs, which is a natural and abundant polymer derived from chitin. Among 15 experimental trials via design expert software, the optimum formula of SE x\CS NPs was prepared at 800 rpm, 5hrs. on magnetic stirrer, and by CS: TPP ratio was 2.5:1. Then SEM showed the majority of particles size diameter in the range of …

Zein And Lignin-Based Nanoparticles As Delivery Systems: Pesticide Release And Nanoparticle Health Impact On Soybean Plants, Fallon Polette Salinas Gonzalez

LSU Doctoral Dissertations

This research examined the effect of biodegradable, polymeric, lignin-based nanoparticles (LNPs, 113.8±3.4, negatively charged) and zein nanoparticles (ZNP, 141.6±3.9, positively charged) on soybean plant health. The LNPs were synthesized from lignin, covalently linked to poly(lactic-co-glycolic) acid by emulsion evaporation. ZNPs were synthesized by nanoprecipitation. Soybeans grown hydroponically were treated with three concentrations (0.02, 0.2, and 2 mg/ml) of NPs at 28 days after germination. The effect of ZNPs and LNPs on plant health was determined through analysis of root and stem length, chlorophyll concentration, dry biomass of roots and stem, as well as carbon, nitrogen, and micronutrient absorption after 1, …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

Overcoming Mechanisms Of Acquired And Innate Doxorubicin Resistance Using Nanomedicine And Tumor-Associated Macrophage Immunotherapy, Rashed M. Almuqbil

Theses and Dissertations

ABSTRACT

Overcoming Mechanisms of Acquired and Innate Doxorubicin Resistance Using Nanomedicine and Tumor-Associated Macrophage Immunotherapy

By Rashed M. Almuqbil, Pharm.D.

Director: Sandro R.P. da Rocha, PhD

Cancer is a leading cause of death worldwide. The available treatment for solid tumors may include surgery, radiotherapy, immunotherapy, and chemotherapy or a combination of all those regimens. Chemotherapy is widely used in the treatment of both lung cancers and breast cancer, including metastases, irrespective of type and stage. The poor rates of survival can be attributed to late diagnosis, and due to the development of acquired and innate chemoresistance. Lung tumors are intrinsically …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

Single-Molecule Investigation Of I-Motif Folding And Dynamics In Bioinspired Dna Platforms, Anoja Megalathan

Theses and Dissertations

Although the canonical right-handed B-DNA is the predominant form of DNA in cells, DNA can adopt other secondary structures such as hairpins, G-quadruplexes (G4), and intercalated motifs (i-motif). These secondary structures are typically formed in the regions with repeat sequences. Among many secondary structures DNA can adopt, G-quadruplexes and i-motifs (tetraplex structures formed in the G-rich and C-rich sequences, respectively) caught significant research interest in recent years due to the prevalence of G-rich and C-rich sequences in the human genome. While G-quadruplexes are extensively studied, little is known about i-motifs – especially their formation and stability under cellular environments. For …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Quantifying Anticancer Drug Doxorubicin Binding To Dna Using Optical Tweezers, Zachary Ells

Honors Program Theses and Projects

Doxorubicin is a successful anticancer drug approved for use in the 1970s and is considered to be one of the most effective cancer treatment methods today. Although Doxorubicin has positive survival statistics it has very negative side effects in many cases. Bleeding from the soles of the palms and feet, along with excruciating pain is often exhibited through the administration of this drug. Based on the preliminary findings utilizing optical tweezers we anticipate that this study will provide critical information about the drug binding mechanism. Single molecule biophysics techniques have provided useful insight into the DNA-binding mechanisms of small molecules. …

Understanding Nanoparticle Toxicity To Direct A Safe-By-Design Approach In Cancer Nanomedicine, Jossana A. Damasco, Saisree Ravi, Joy D. Perez, Daniel E. Hagaman, Marites P. Melancon

School of Medicine Publications

Nanomedicine is a rapidly growing field that uses nanomaterials for the diagnosis, treatment and prevention of various diseases, including cancer. Various biocompatible nanoplatforms with diversified capabilities for tumor targeting, imaging, and therapy have materialized to yield individualized therapy. However, due to their unique properties brought about by their small size, safety concerns have emerged as their physicochemical properties can lead to altered pharmacokinetics, with the potential to cross biological barriers. In addition, the intrinsic toxicity of some of the inorganic materials (i.e., heavy metals) and their ability to accumulate and persist in the human body has been a challenge to …

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) …

Comprehensive Review On Current Interventions, Diagnostic, And Nanotechnology Perspectives Against Sars-Cov-2, Deepak S. Chauhan, Rajendra Prasad, Rohit Srivastava, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

COVID-19 has dramatically challenged the healthcare system of almost all countries. The authorities are struggling to minimize the mortality along with ameliorating the economy downturn. Unfortunately, till now, there has been no promising medicine or vaccine available. Herein, we deliver a perspective of nanotechnology for increasing the specificity and sensitivity of current interventional platforms towards the urgent need of quickly deployable solutions. This review summarizes the recent involvement of nanotechnology from the development of biosensor to fabrication of multifunctional nanohybrid system practiced for respiratory and deadly viruses, along with the recent interventions and current understanding about SARS-CoV2.

Nature-Inspired Electrode Materials For Next Generation Sustainable Energy Storage, Mikhail Miroshnikov

Dissertations, Theses, and Capstone Projects

Despite revolutionizing the world of portable electronics, the contemporary lithium-ion battery (LIB) suffers from challenges associated with the cost, safety, and environmental impact of transition metal oxide-based intercalation cathodes. To alleviate these issues, naturally occurring organic molecules may serve as sustainable alternatives to traditional inorganic cathode materials. The electrochemical properties of organic compounds are derived from redox-active functional groups containing oxygen, nitrogen and sulfur. Additionally, these functional groups are capable of coordinating metal ions beyond lithium, allowing for compatibility with sodium-ion batteries (SIBs) and other earth abundant metal-based energy storage systems. However, despite competitive performance against commercialized cathode materials, much …

Chrysin‐Loaded Chitosan Nanoparticles Potentiates Antibiofilm Activity Against Staphylococcus Aureus, Busi Siddhardha, Uday Pandey, K. Kaviyarasu, Rajasekharreddy Pala, Asad Syed, Ali K. Bahkali, Abdallah M. Elgorban

Pharmacy Faculty Articles and Research

The application of nanotechnology in medicine is gaining popularity due to its ability to increase the bioavailability and biosorption of numerous drugs. Chrysin, a flavone constituent of Orocylumineicum vent is well‐reported for its biological properties. However, its therapeutic potential has not been fully exploited due to its poor solubility and bioavailability. In the present study, chrysin was encapsulated into chitosan nanoparticles using TPP as a linker. The nanoparticles were characterized and investigated for their anti‐biofilm activity against Staphylococcus aureus. At sub‐Minimum Inhibitory Concentration, the nanoparticles exhibited enhanced anti‐biofilm efficacy against S. aureus as compared to its bulk counterparts, chrysin …

Engineering Hyaluronic Acid For Biomedical Applications, Deep S. Bhattacharya

Theses & Dissertations

This work presents research using the naturally available non- sulfated carbohydrate glycosaminoglycan hyaluronic acid (HA) for the synthesis of different chemical derivatives of HA for evaluation of binding kinetics with CD44 and P- selectin proteins for applications in fluorescence image-guided surgery. Chemical derivatives of HA such as deacetylated HA (deHA), sulfated HA (sHA), and deacetylated and sulfated HA (s-deHA) were synthesized by modulating sulfating and deacetylating reagents to alter binding specificities to CD44. Modified HA derivatives and CD44 biophysical interactions were assessed by fluorescence polarization. In silico techniques were also used to determine binding using molecular docking and MM-PBSA approaches. …

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Gemcitabine Combination Nano Therapies For Pancreatic Cancer, Kamalika Samanta, Saini Setua, Sonam Kumari, Meena Jaggi, Murali Yallapu, Subhash C. Chauhan

School of Medicine Publications

Pancreatic cancer is one of the deadliest causes of cancer-related death in the United States, with a 5-year overall survival rate of 6 to 8%. These statistics suggest that immediate medical attention is needed. Gemcitabine (GEM) is the gold standard first-line single chemotherapy agent for pancreatic cancer but, after a few months, cells develop chemoresistance. Multiple clinical and experimental investigations have demonstrated that a combination or co-administration of other drugs as chemotherapies with GEM lead to superior therapeutic benefits. However, such combination therapies often induce severe systemic toxicities. Thus, developing strategies to deliver a combination of chemotherapeutic agents more securely …

Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly

Dissertations, Theses, and Capstone Projects

The potency and specificity of bioactive peptides have propelled these agents to the forefront of pharmacological research. However, delivery of peptides to their molecular target in cells is a major obstacle to their widespread application. A Trojan Horse strategy of packaging a bioactive peptide within a modified protein cage to protect it during transport, and releasing it at the target site, is a promising delivery method. Recent work has demonstrated that the viral capsid of the P22 bacteriophage can be loaded with an arbitrary, genetically-encoded peptide, and externally decorated with a cell-penetrating peptide, such as HIV-Tat, to translocate across in …

A Robust Delivery System For Rna Therapeutics, Suleyman Bozal

University Scholar Projects

The field of RNA therapeutics is currently undergoing both transformation and expansion. Specifically, research in lipid nanoparticle (LNP) based RNA therapeutics is gaining significant traction. Other research into mechanisms of gene regulation and manipulation, including siRNA and the CRISPR/Cas9 system have demonstrated the potential of RNA-based disease treatment. This work identifies a delivery system which can regulate expression of green fluorescent protein (GFP) in human embryonic kidney cells (HEK293) stably expressing GFP.

Analysis of siRNA-induced gene knockdown demonstrates that the current siRNA-LNP formulation is equally as effective as a commercially available transfection reagent, Lipofectamine RNAiMAX (RNAiMAX), which is designed specifically …

A Robust Delivery System For Rna Therapeutics, Suleyman Bozal

Honors Scholar Theses

The field of RNA therapeutics is currently undergoing both transformation and expansion. Specifically, research in lipid nanoparticle (LNP) based RNA therapeutics is gaining significant traction. Other research into mechanisms of gene regulation and manipulation, including siRNA and the CRISPR/Cas9 system have demonstrated the potential of RNA-based disease treatment. This work identifies a delivery system which can regulate expression of green fluorescent protein (GFP) in human embryonic kidney cells (HEK293) stably expressing GFP.

Analysis of siRNA-induced gene knockdown demonstrates that the current siRNA-LNP formulation is equally as effective as a commercially available transfection reagent, Lipofectamine RNAiMAX (RNAiMAX), which is designed specifically …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Mechanisms And Thermodynamics Of The Influence Of Solution-State Interactions Between Hpmc And Surfactants On Mixed Adsorption Onto Model Nanoparticles, Salin Gupta Patel

Theses and Dissertations--Pharmacy

Nanoparticulate drug delivery systems (NDDS) such as nanocrystals, nanosuspensions, solid-lipid nanoparticles often formulated for the bioavailability enhancement of poorly soluble drug candidates are stabilized by a mixture of excipients including surfactants and polymers. Most literature studies have focused on the interaction of excipients with the NDDS surfaces while ignoring the interaction of excipients in solution and the extent to which the solution-state interactions influence the affinity and capacity of adsorption. Mechanisms by which excipients stabilize NDDS and how this information can be utilized by formulators a priori to make a rational selection of excipients is not known.

The goals of …

Combination Therapy: Parp Inhibitor Synergizes The Therapeutic Efficacy Of Doxorubicin In The Treatment Of Prostate Cancer, Momin Ansare

Electronic Theses & Dissertations

Men are most susceptible to prostate cancer in the United States. The general treatment options include surgery, hormone therapy, chemotherapy, and radiation therapy. But in recent days, the nanoformulation have shown promising applications in overcoming the drawbacks of the currently available treatment options. To complement, we tried to enhance the capability of the nanoparticle formulation by loading them with a novel drug combination for the treatment of prostate cancer. Herein, we synthesized folate conjugated iron oxide nanoparticles encapsulated with doxorubicin and olaparib for imaging and targeted treatment of prostate cancer. Both drugs are approved by FDA for clinical cancer treatment. …

Distribution And Localization Of Novel Iodine Nanoparticles In The Human Glioma 1242 Growing In The Brains Of Mice, Benjamin Billings

Honors Scholar Theses

Observing and designing the in vivo distribution and localization of therapeutic nanoparticles is an essential aspect of developing and understanding novel nanoparticle- based medical treatments. This study investigates novel PEGylated Iodine-based nanoparticles (INPs), an alternate composition to the more widely researched gold nanoparticles (AuNPs), which may help avoid adverse effects associated with AuNPs, such as potential toxicity and skin discoloration, when used in similar applications. Determining the localization of the novel INPs within murine brains containing human glioma U-1242MG cells is critical in assisting the development of radiation dose enhancement therapy for this aggressive cancer. Radiation dose enhancement utilizes the …

Bacterial Lps At The Immune Modulating Component In Juzen-Taiho-To, Diego Montenegro

Dissertations, Theses, and Capstone Projects

Juzen-taiho-to (JTT) is an immune-boosting herbal formulation with an ideal balance of safety and efficacy. For example, JTT is clinically used in Japan to stimulate the immunological functions of cancer patients undergoing chemotherapy and radiation. Although the clinical effects of JTT are recognized, the active compounds and mechanism of action are unknown. The studies conducted previously in our laboratory associated several phytosterols and plant glycolipids with the potent immunostimulatory activity of JTT: namely, β-sitosteryl β-D-glucoside (BSSG), glucocerebroside (GluCer), digalactosyldiacylglycerol (DGDG) and monogalactosyldiacylglycerol (MGDG). However, these compounds, when further purified, exhibited little or no immunostimulatory activity. This suggested that the immunostimulatory …

Hyperthermia As A Cancer Treatment- From Theory To Practice, Graham Fullerton

CMC Senior Theses

Using iron super-paramagnetic and ferromagnetic nanoparticles composed of Fe₃O₄ molecules, scientists analyze the effectiveness and practicality of this new treatment theory, hyperthermia. The problems of magnetic particle density, isothermal barriers/cellular cooling thresholds, and nanoparticle specific targeting are addressed in this review.

Iron magnetic nanoparticles were chosen due to their relatively low biological reactivates and lack of subsequent cellular toxicity. However, there are significant heating problems associated with these magnetic nanoparticles due to their relative size and short thermal time constants or thermal half-lives. Effectively, these aforementioned issues create a phenomenon where cancerous cells, surrounded by unheated healthy …

Nano-Strategies To Fight Multidrug Resistant Bacteria—“A Battle Of The Titans", Pedro V. Baptista, Matthew P. Mccusker, Andreia Carvalho, Daniela A. Ferreira, Niamh M. Mohan, Marta Martins, Alexandra R. Fernandez

Articles

Infectious diseases remain one of the leading causes of morbidity and mortality worldwide. The WHO and CDC have expressed serious concern regarding the continued increase in the development of multidrug resistance among bacteria. Therefore, the antibiotic resistance crisis is one of the most pressing issues in global public health. Associated with the rise in antibiotic resistance is the lack of new antimicrobials. This has triggered initiatives worldwide to develop novel and more effective antimicrobial compounds as well as to develop novel delivery and targeting strategies. Bacteria have developed many ways by which they become resistant to antimicrobials. Among those are …

Size, Shape, And Sequence-Dependent Immunogenicity Of Rna Nanoparticles, Sijin Guo, Hui Li, Mengshi Ma, Jian Fu, Yizhou Dong, Peixuan Guo

Center for Research on Environmental Disease Faculty Publications

RNA molecules have emerged as promising therapeutics. Like all other drugs, the safety profile and immune response are important criteria for drug evaluation. However, the literature on RNA immunogenicity has been controversial. Here, we used the approach of RNA nanotechnology to demonstrate that the immune response of RNA nanoparticles is size, shape, and sequence dependent. RNA triangle, square, pentagon, and tetrahedron with same shape but different sizes, or same size but different shapes were used as models to investigate the immune response. The levels of pro-inflammatory cytokines induced by these RNA nanoarchitectures were assessed in macrophage-like cells and animals. It …