Pharmacy and Pharmaceutical Sciences Commons^™

Solid Lipid Nanoparticles (Sln): Formulation And Fabrication, Gabriella F. Punu, Yahdiana Harahap, Qonita Kurnia Anjani, Pietradewi Hartrianti, Ryan F. Donnelly, Delly Ramadon

Pharmaceutical Sciences and Research

Solid lipid nanoparticles (SLN) have emerged as a novel drug delivery system and have been utilized for delivering various kinds of drugs since the 1990s. These particles may consist of multiple solid lipids, including glycerides, waxes, and fatty acids, and can be stabilized by a wide range of surfactants. SLN have garnered significant attention from researchers due to its innovative and versatile nature. Moreover, such delivery system has numerous advantages over traditional colloidal carriers, such as liposomes, polymeric nanoparticles, and emulsions. Several research groups have been developing SLN formulations and fabrication techniques based on their intended purpose, and this research …

Effect Of Nanoparticle Weight On The Cellular Uptake And Drug Delivery Potential Of Plga Nanoparticles, Prabhat Kattel, Shoukath Sulthana, JiřÍ Trousil, Dinesh Shrestha, David Pearson, Santosh Aryal

Pharmacy Faculty Publications and Presentations

Biodegradable and biocompatible polymeric nanoparticles (NPs) stand out as a key tool for improving drug bioavailability, reducing the inherent toxicity, and targeting the intended site. Most importantly, the ease of polymer synthesis and its derivatization to add functional properties makes them potentially ideal to fulfill the requirements for intended therapeutic applications. Among many polymers, US FDA-approved poly(L-lactic-co-glycolic) acid (PLGA) is a widely used biocompatible and biodegradable co-polymer in drug delivery and in implantable biomaterials. While many studies have been conducted using PLGA NPs as a drug delivery system, less attention has been given to understanding the effect of NP weight …

Nanoparticle Approaches For The Renin-Angiotensin System, Sajini D. Hettiarachchi, Young M. Kwon, Yadollah Omidi, Robert C. Speth

HPD Articles

The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders: systemic hypertension, heart failure, kidney disease, and neurodegenerative disease. Activation of the RAS can promote inflammation and fibrosis. Drugs that target the RAS can be classified into 3 categories, AT1 angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic efficacy of current RAS-inhibiting drugs is limited by poor penetration across the blood-brain barrier, low bioavailability, and to some extent, short half-lives. Nanoparticle-mediated drug delivery systems (DDSs) are possible emerging alternatives to overcome such limitations. Nanoparticles are ideally 1-100 nm in size and are …

Exploring The Potential Of Nanotechnology In Pediatric Healthcare: Advances, Challenges, And Future Directions., Hossein Omidian, Kwadwo Mfoafo

HPD Articles

The utilization of nanotechnology has brought about notable advancements in the field of pediatric medicine, providing novel approaches for drug delivery, disease diagnosis, and tissue engineering. Nanotechnology involves the manipulation of materials at the nanoscale, resulting in improved drug effectiveness and decreased toxicity. Numerous nanosystems, including nanoparticles, nanocapsules, and nanotubes, have been explored for their therapeutic potential in addressing pediatric diseases such as HIV, leukemia, and neuroblastoma. Nanotechnology has also shown promise in enhancing disease diagnosis accuracy, drug availability, and overcoming the blood-brain barrier obstacle in treating medulloblastoma. It is important to acknowledge that while nanotechnology offers significant opportunities, there …

Evaluation Of Selenomethionine Entrapped In Nanoparticles For Oral Supplementation Using In Vitro, Ex Vivo And In Vivo Models, Shane Forde, Giuliana Vozza, David J. Brayden, Jesus Maria Frias, Sinead M. Ryan

Articles

Selenium methionine (Se Met) is an essential micronutrient required for normal body function and is associated with additional health benefits. However, oral administration of Se Met can be challenging due to its purported narrow therapeutic index, low oral bioavailability, and high susceptibility to oxidation. To address these issues, Se Met was entrapped in z e i n-coated nanoparticles made from chitosan using an ionic gelation formulation. The high stability of both the Se Met and s e l e n o methionine nanoparticles (Se Met-NPs) was established using cultured human intestinal and liver epithelial cells, rat liver homogenates, and rat …

Nanoparticles For Biomedical Applications, Joseph Kim

Dissertations & Theses (Open Access)

This thesis presents development and evaluation of the potential of three new nanoparticles for biomedical applications. With the rapid growth of the field of nanoscience, researchers have explored developing nanoparticles for various biomedical applications, including imaging, therapy, and drug delivery. This thesis demonstrates the development of two C­₆₀ fullerene based nanoparticles and one boron based nanoparticle to answer key questions related to their biological potential.

In the first part of the thesis, we describe synthesis and characterization of a pure boron nanoparticle containing asolectin phospholipid-based liposome construct prepared using a water-in-oil emulsion method, as a novel alternative agent for …

Indocyanine-Type Infrared-820 Encapsulated Polymeric Nanoparticle-Assisted Photothermal Therapy Of Cancer, Ramesh Marasini, Santosh Aryal

Pharmacy Faculty Publications and Presentations

Organic small-molecule photosensitizers are well-characterized and known for the light-responsive treatment modality including photodynamic therapy. Compared with ultraviolet−visible (UV−vis) light used in conventional photodynamic therapy with organic photosensitizers, near-infrared (NIR) light from 700 to 900 nm is less absorbed and scattered by biological tissue such as hemoglobin, lipids, and water, and thus, the use of NIR excitation can greatly increase the penetration depth and emission. Additionally, NIR light has lower energy than UV−vis that can be beneficial due to less activation of fluorophores present in tissues upon NIR irradiation. However, the low water stability, nonspecific distribution, and short circulation halflife …

Direct Nose To The Brain Nanomedicine Delivery Presents A Formidable Challenge, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

This advanced review describes the anatomical and physiological barriers and mechanisms impacting nanomedicine translocation from the nasal cavity directly to the brain. There are significant physiological and anatomical differences in the nasal cavity, olfactory area, and airflow reaching the olfactory epithelium between humans and experimentally studied species that should be considered when extrapolating experimental results to humans. Mucus, transporters, and tight junction proteins present barriers to material translocation across the olfactory epithelium. Uptake of nanoparticles through the olfactory mucosa and translocation to the brain can be intracellular via cranial nerves (intraneuronal) or other cells of the olfactory epithelium, or extracellular …

Cd44-Targeted, Indocyanine Green-Paclitaxel-Loaded Human Serum Albumin Nanoparticles For Potential Image-Guided Drug Delivery., Karthik Thangavel, Asha Lakshmikuttyamma, Chellappagounder Thangavel, Sunday A. Shoyele

College of Pharmacy Faculty Papers

The use of multifunctional nanomedicines for image-guided drug delivery is currently being universally evaluated as a means of efficiently managing cancers and other diseases. In this study we evaluated the potential of an indocyanine green (ICG) and paclitaxel (PTX) loaded human serum albumin (HSA) nanoparticles that was conjugated with hyaluronic acid for use in image-guided drug delivery targeted to CD44-positive non-small cell lung cancer (NSCLC). Series of NSCLC cell lines were evaluated for the expression of CD44 using both western blot analysis and qRT-PCR and compared to a normal lung fibroblast cell line (MRC-5). Using Fluorescence microscopy and photoacoustic imaging …

The Preparation Temperature Influences The Physicochemical Nature And Activity Of Nanoceria, Robert A. Yokel, Wendel Wohlleben, Johannes Georg Keller, Matthew L. Hancock, Jason M. Unrine, D. Allan Butterfield, Eric A. Grulke

Pharmaceutical Sciences Faculty Publications

Cerium oxide nanoparticles, so-called nanoceria, are engineered nanomaterials prepared by many methods that result in products with varying physicochemical properties and applications. Those used industrially are often calcined, an example is NM-212. Other nanoceria have beneficial pharmaceutical properties and are often prepared by solvothermal synthesis. Solvothermally synthesized nanoceria dissolve in acidic environments, accelerated by carboxylic acids. NM-212 dissolution has been reported to be minimal. To gain insight into the role of high-temperature exposure on nanoceria dissolution, product susceptibility to carboxylic acid-accelerated dissolution, and its effect on biological and catalytic properties of nanoceria, the dissolution of NM-212, a solvothermally synthesized nanoceria …

Copper Oxide Nanoparticle Diameter Mediates Serum-Sensitive Toxicity In Beas-2b Cells, Angie S. Morris, Brittany E. Givens, Aaron Silva, Aliasger K. Salem

Chemical and Materials Engineering Faculty Publications

Copper oxide (CuO) nanoparticles (NPs) are abundant in manufacturing processes, but they are an airway irritant. In vitro pulmonary toxicity of CuO NPs has been modeled using cell lines such as human bronchial epithelial cell line BEAS-2B. In 2D in vitro culture, BEAS-2B undergoes squamous differentiation due to the presence of serum. Differentiation is part of the repair process of lung cells in vivo that helps to preserve the epithelial lining of the respiratory tract. Herein, the effects of serum on the hydrodynamic diameter, cellular viability, cellular differentiation, and cellular uptake of 5 and 35 nm CuO NPs are investigated, …

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 …

Exploring Efficacy Of An Anti-Malarial Nanomedicine In Non-Small Cell Lung Cancer Treatment, Vineela Parvathaneni

Theses and Dissertations

New drug and dosage form development faces significant challenges, especially in oncology, due to longer development cycle and associated scale-up complexities. Repurposing of existing drugs with potential anti-cancer activity into new therapeutic regimens provides a feasible alternative. In this project, amodiaquine (AQ), an anti-malarial drug, has been explored for its anti-cancer efficacy through formulating inhalable nanoparticulate systems using high-pressure homogenization (HPH) with scale-up feasibility and high reproducibility. A 32 multifactorial design was employed to better understand critical processes and formulation parameters so as to ensure product quality with improved anticancer efficacy in non-small cell lung cancer (NSCLC). Optimized AQ loaded …

Double-Coated Biodegradable Poly (Butyl Cyanoacrylate) Nanoparticulate Delivery Systems For Brain Targeting Of Doxorubicin Via Oral Administration, Neeraj Kaushal

Theses and Dissertations

Primary brain cancer cells grow within the brain or cancer cells can metastasis from different site of the body into brain. The major hurdle in the treatment of brain cancer is the presence of blood-brain barrier (BBB). Additionally, acquired multidrug-resistant (MDR) impedes the success of long-term chemotherapy. Therefore, the objective of this investigation is to evaluate the brain targeting potential of orally administered poly(butyl cyanoacrylate) nanoparticulate delivery systems (PBCA-NPDS), double-coated with Tween 80 and polyethylene glycol (PEG) 20000 for brain delivery of doxorubicin, that does not cross the BBB by itself. And, evaluate the MDR reversal potential of PBCA-NPDS. Doxorubicin-loaded …

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 …

Rna Nanoparticles And Method Of Use Thereof, Peixuan Guo, Hui Li, Wei Luo

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter relates to an artificial RNA nanostructure and method of use thereof. In particular, the presently-disclosed subject matter relates to RNA nanoparticles and RNA dendrimers, and methods of disease diagnosis and treatments using the RNA nanostructure and RNA dendrimers.

Nanoceria Distribution And Effects Are Mouse-Strain Dependent, Robert A. Yokel, Michael T. Tseng, D. Allan Butterfield, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Arnold J. Stromberg, Alan K. Dozier, Uschi M. Graham

Pharmaceutical Sciences Faculty Publications

Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. Objective: Assess nanoceria (cerium oxide, CeO₂ nanoparticle) uptake time course and organ distribution, cellular and oxidative stress, and bioprocessing as a function of mouse strain. Methods: C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. Organs were collected for cerium analysis; light and electron microscopy with elemental mapping; and protein carbonyl, IL-1β, and caspase-1 determination. Results: Peripheral organ cerium significantly increased, generally more …

Synthesizing Modified Polymeric Nanoparticles For Biofilm Inhibition, Antibiotic Encapsulation, And Specific Targeting Against Pseudomonas Aeruginosa, Logan Schnorbus

Theses and Dissertations

Widespread usage of antibiotics is a growing concern due to antibiotic resistance development in bacteria. This is due to common use of antibiotics in agricultural, livestock, and clinical usage. Antibiotic resistance is developing at a rate in which it is outpacing new drugs on the market. New strategies in drug development are necessary to combat the increasing resistance. We designed several motifs of sugar-modified nanoparticles to inhibit the biofilm formation of Pseudomonas aeruginosa.

P. aeruginosa is an opportunistic pathogenic bacterium that is responsible for common life-threatening infection in hospitals. This gram-negative opportunistic pathogenic bacterium infects hosts with compromised immune systems …

Nanoparticle-Mediated Drug Delivery For The Treatment Of Cardiovascular Diseases, Rajasekharreddy Pala, Vt Anju, Madhu Dyavaiah, Siddhardha Busi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Cardiovascular diseases (CVDs) are one of the foremost causes of high morbidity and mortality globally. Preventive, diagnostic, and treatment measures available for CVDs are not very useful, which demands promising alternative methods. Nanoscience and nanotechnology open a new window in the area of CVDs with an opportunity to achieve effective treatment, better prognosis, and less adverse effects on non-target tissues. The application of nanoparticles and nanocarriers in the area of cardiology has gathered much attention due to the properties such as passive and active targeting to the cardiac tissues, improved target specificity, and sensitivity. It has reported that more than …

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …

Novel Paclitaxel Nanoparticles For Enhanced Therapeutic Effects In Breast Cancer, Pallabita Chowdhury

Theses and Dissertations (ETD)

Drug delivery to triple negative breast cancer (TNBC) remains a formidable challenge. Given the lack of expressions of estrogen (ER), progesterone (PR) and human epidermal growth factor receptor (HER2), there is no specific prognostic marker for targeting this aggressive cancer. In spite of rapid advancement in breast cancer with agents such as Trastuzumab in HER2 positive, chemotherapy with cytotoxic agents remains the mainstay treatment for TNBC. Although these cytotoxic agents are potent in managing the tumor progression, yet they pose adverse effects on healthy tissues. Paclitaxel (PTX) has been used as a gold standard chemotherapeutic agent for breast, ovarian, pancreatic …

Rna Nanoparticles For Brain Tumor Treatment, Peixuan Guo, Carlo M. Croce, Tae Jin Lee, Farzin Haque, Hui Li

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter relates to an artificial RNA nanostructure molecule and method to treat brain tumor in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure containing a multiple branched RNA nanoparticle, a brain tumor targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanostructure composition to treat brain tumor in a subject having or at risk of having brain tumor.

Formulation Strategies To Enhance Solubility And Permeability Of Small Molecules For Drug Delivery Applications, Pradeep Kumar Bolla

Open Access Theses & Dissertations

All the new chemical entities/drug molecules intended for therapeutic use must be administered using an appropriate delivery system/dosage form to achieve maximum bioavailability. However, designing a drug delivery system is complex as several factors such as lipophilicity, molecular mass, crystallinity, ionic charge, polymorphic forms and hydrogen bonding) affect the solubility and permeability of these molecules. Biopharmaceutics drug classification system (BCS) categorizes the existing drugs into four classes based on the aqueous solubility and membrane permeability and it is reported that >70% of the drugs are poorly soluble and belong to BCS class II and BCS class IV. Several physical, chemical …

Development And Characterization Of Ldv Peptide Targeted Nanocarriers For Paclitaxel Delivery: A Comparative Study Of Micelles, Liposomes And Solid Lipid Nanoparticles, Poonam Dattani

University of the Pacific Theses and Dissertations

Nanocarriers have been established as delivery vehicles to target cancer tumors. However, premature drug leakage is one of the major reasons for inefficient drug delivery of nanocarriers to the tumor. Drug diffusion out of the nanocarriers or destabilization of drug loaded nanocarriers by physiological interactions with blood cells, serum proteins, and cell membranes upon systemic administration contribute to premature drug release. In this study, targeted micelles, liposomes and solid lipid nanoparticles (SLNs) of similar composition were prepared and characterized to compare physicochemical characteristics, in vitro stability, in vitro release rates in release media and in vivo performance. Peptide Amphiphiles (PAs) …

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 …

Delivery Of Microrna With Cxcr4-Targeted Nanoparticles In Metastatic Cancer Treatment, Ying Xie

Theses & Dissertations

Metastasis is the main contributor to cancer-associated deaths. Inhibition of CXCR4 emerged as one promising approach in metastatic cancer therapy. MiRNAs represent a new class of therapeutics for cancer treatment through RNA interference-mediated gene silencing. Polymeric CXCR4 antagonist (PCX) is a dual-functional polycation to inhibit CXCR4 and deliver nucleic acids. This dissertation hypothesized that blockade of CXCR4 by PCX combined with delivery of miRNA cooperatively enhances metastatic cancer therapy.

In chapter 1, an overview of CXCR4 inhibition, miRNA delivery and CXCR4 targeted nanomedicine in cancer therapy is given.

Chapter 2 reports that PCX can effectively deliver miR-200c mimic and that …

Morphometric Characteristics And Time To Hatch As Efficacious Indicators For Potential Nanotoxicity Assay In Zebrafish, Seyed-Mohammadreza Samaee, Nafiseh Manteghi, Robert A. Yokel, Mohammad Reza Mohajeri-Tehrani

Pharmaceutical Sciences Faculty Publications

Although the effects of nano-sized titania (nTiO₂) on hatching events (change in hatching time and total hatching) in zebrafish have been reported, additional consequences of nTiO₂ exposure (i.e., the effects of nTiO₂-induced changes in hatching events and morphometric parameters on embryo-larvae development and survivability) have not been reported. To address this knowledge gap, embryos 4 h postfertilization were exposed to nTiO₂ (0, 0.01, 10, and 1000 μg/mL) for 220 h. Hatching rate (58, 82, and 106 h postexposure [hpe]), survival rate (8 times from 34 to 202 hpe), and 21 morphometric characteristics (8 times …

Physiologically Based Pharmacokinetic Modeling Of Nanoceria Systemic Distribution In Rats Suggests Dose- And Route-Dependent Biokinetics, Ulrika Carlander, Tshepo Paulsen Moto, Anteneh Assefa Desalegn, Robert A. Yokel, Gunnar Johanson

Pharmaceutical Sciences Faculty Publications

Background: Cerium dioxide nanoparticles (nanoceria) are increasingly being used in a variety of products as catalysts, coatings, and polishing agents. Furthermore, their antioxidant properties make nanoceria potential candidates for biomedical applications. To predict and avoid toxicity, information about their biokinetics is essential. A useful tool to explore such associations between exposure and internal target dose is physiologically based pharmacokinetic (PBPK) modeling. The aim of this study was to test the appropriateness of our previously published PBPK model developed for intravenous (IV) administration when applied to various sizes of nanoceria and to exposure routes relevant for humans.

Methods: Experimental biokinetic data …

Cerium Oxide Nanoparticle Aggregates Affect Stress Response And Function In Caenorhabditis Elegans, Steven Rogers, Kevin M. Rice, Nandini Manne, Tolou Shokuhfar, Kun He, Vellaisamy Selvaraj, Eric Blough

Eric Blough

Objective: The continual increase in production and disposal of nanomaterials raises concerns regarding the safety of nanoparticles on the environmental and human health. Recent studies suggest that cerium oxide (CeO2) nanoparticles may possess both harmful and beneficial effects on biological processes. The primary objective of this study is to evaluate how exposure to different concentrations (0.17–17.21 µg/mL) of aggregated CeO2 nanoparticles affects indices of whole animal stress and survivability in Caenorhabditis elegans.

Methods: Caenorhabditis elegans were exposed to different concentrations of CeO2 nanoparticles and evaluated.

Results: Our findings demonstrate that chronic exposure of CeO2 nanoparticle aggregates is …

Cerium Oxide Nanoparticle Aggregates Affect Stress Response And Function In Caenorhabditis Elegans, Steven Rogers, Kevin M. Rice, Nandini Manne, Tolou Shokuhfar, Kun He, Vellaisamy Selvaraj, Eric Blough

Nandini Manne

Objective: The continual increase in production and disposal of nanomaterials raises concerns regarding the safety of nanoparticles on the environmental and human health. Recent studies suggest that cerium oxide (CeO2) nanoparticles may possess both harmful and beneficial effects on biological processes. The primary objective of this study is to evaluate how exposure to different concentrations (0.17–17.21 µg/mL) of aggregated CeO2 nanoparticles affects indices of whole animal stress and survivability in Caenorhabditis elegans.

Methods: Caenorhabditis elegans were exposed to different concentrations of CeO2 nanoparticles and evaluated.

Results: Our findings demonstrate that chronic exposure of CeO2 nanoparticle aggregates is …