Chemicals and Drugs Commons^™

Recent Progress In Nanogel Technology: From Molecular Design To Biomedical Applications, Fatima Raed Al-Ahmed, Mohammed Sabar Al-Lami

Maaen Journal for Medical Sciences

Nanogels, a hydrophilic polymer network at the nanoscale, combine the structural flexibility of hydrogels with the dynamic behavior of nanoparticles, offering unprecedented control over drug loading and release. Their large surface area, tunable porosity, high water content, biocompatibility, and stimuli-responsive behavior enable transport across biological barriers. This review critically examines nanogels’ unique properties, classifications, diverse methods of preparation, drug release mechanisms, characterization techniques, and various applications in therapeutic areas, such as cancer therapy, wound healing, transdermal and ocular drug delivery, and theranostics. Highlights are shed on nanogels’ potential to target specific sites, both by functionalization and stimuli-responsive behavior, therefore improving …

Tumor Targeting With Peptide-Drug Conjugates: Showcasing Key Progress And Hurdles, Keykavous Parang, Thuy Do, Clare Dinh, Dorna Davanidavari, Max Foroughi, Troy Khong, Mahsa Moazen, Amir Nasrolahi Shirazi

Pharmacy Faculty Articles and Research

Peptide-drug conjugates (PDCs) are modular, targeted therapeutics composed of a homing peptide linked to a cytotoxic or modulating drug payload via a cleavable/non-cleavable linker. PDCs utilize peptide targeting to enhance the delivery of potent drugs to tumors, providing advantages such as superior tissue penetration, reduced immunogenicity, and simpler manufacture compared to antibody-drug conjugates (ADCs). A comparison of PDCs versus ADCs highlights that PDCs’ small size (~1-3 kDa) enables deeper tumor penetration and faster clearance, whereas ADCs (~150 kDa) benefit from prolonged circulation but suffer from limited tissue diffusion. This review surveys recent advances in PDC design and application. We discuss …

Reverse Micelles Produce Hydroxyapatite Nanoparticles As More Efficient Gene Delivery Carriers Than Regular Micelles, Vuk Uskoković

Administration and Staff Articles and Research

Hydroxyapatite (HAp) is an effective inorganic gene delivery carrier due to its ability to transport genetic cargo across cell membranes, protect it from proteolysis, and enable escape from late endosomes via pH-controlled dissolution. However, its transfection efficiency remains lower than that of viral agents, prompting studies of hybrids with cationic molecules or phases to enhance the gene delivery performance. This study reports on the synthesis of HAp in regular and reverse micellar regions of a ternary microemulsion system composed of cetyltrimethylammonium bromide (CTAB), 1-hexanol and water. Spectroscopic characterization revealed that CTAB headgroups adopted more ordered supramolecular conformations in reverse micelles …

Engineered Bifidobacterium Strains Colonization At Tumor Sites: A Novel Approach To The Delivery Of Cancer Treatments, Rhea Amonkar, Ashley Ann Uy, Pablo Ramirez, Harina Patel, Jae Jin Jeong, Nicole Oyinade Shoyele, Vidhi Vaghela, Ashakumary Lakshmikuttyamma

College of Pharmacy Faculty Papers

Bacteria-mediated cancer therapy represents a novel and promising strategy for targeted drug delivery to solid tumors. Multiple studies have demonstrated that various Bifidobacterium species can selectively colonize the hypoxic microenvironments characteristic of solid tumors. Leveraging this property, Bifidobacterium has been explored as a delivery vector for a range of anti-cancer approaches such as immunotherapy, nanoformulated chemothera- peutics, and gene therapy. Notably, anti-angiogenic genes such as endostatin and tumstatin have been successfully delivered to colorectal tumors using Bifidobacterium infantis and Bifidobacterium longum, respectively. Additionally, Bifidobacterium bifidum has been employed to transport doxorubicin and paclitaxel nanoparticles to breast and lung tumor …

Mechanistic Investigation Of Ring-Opening Polymerization Of Polycaprolactone Using Tin(Ii) Catalysts: Ligand Effects And Biomedical Applications, Eva-Larue M. Barber

Honors Scholar Theses

This research explores the mechanistic aspects of ring-opening polymerization (ROP) of ε-caprolactone (CL) to produce polycaprolactone (PCL), a biodegradable polymer widely used in biomedical applications. The study investigates how light exposure and catalyst concentration influence polymerization efficiency, using tin(II) 2-ethylhexanoate [Sn(Oct)₂] as the catalyst in a non-polar toluene solvent at 90 °C. Reactions were conducted under either ambient light or black light bulb (BLB) illumination, with monomer-to-catalyst ratios of 1:1 and 200:1.

Proton nuclear magnetic resonance (¹H NMR) spectroscopy was used to analyze conversion efficiency by tracking the disappearance of monomer signals and appearance of characteristic PCL peaks. Results revealed …

Improving Niclosamide's Effectiveness In Cancer Therapy: Advances In Drug Modification And Delivery, Russell Wiggins, Jihoo Woo, Shizue Mito

Research Symposium

The property of niclosamide to inhibit multiple cancer-related pathways has made it a promising candidate for the treatment of various cancers. However, poor bioavailability and solubility have significantly restricted its clinical application. This literature review explores various strategies that enhance the bioavailability and efficacy of Niclosamide through the development of Niclosamide derivatives and the utilization of drug delivery systems. We also briefly discuss Niclosamide’s suspected mechanisms of action in several cancer related pathways. Derivatives such as Niclosamide Ethanolamine (NEN) and Niclosamide Piperazine (NPP) have demonstrated improved pharmacokinetic properties, including increased solubility and bioavailability, without compromising anticancer activity. Importantly, these formulations …

Magnetic And Ph-Sensitive Dual Actuation Of Biohybrid Microswimmer Of Targeted Drug Release Suitable For Cancer Cell Microenvironment, Richa Chaturvedi, Yumin Kang, Yunji Eom, Sri Ramulu Torati, Cheolgi Kim

Center for Bioelectronics Publications

The chemotherapeutic agents most frequently used in cancer treatment often have limited effectiveness because of their low specificity for tumors and poor therapeutic performance. In addition to the aforementioned therapeutic challenges the drug delivery carriers conjugated with the drug encounter early detection and elimination from the immune system before arriving at the affected area continues to be a significant research focus among researchers. To address this prevalent issue, an effective approach has been developed that leverages the physiological differences between normal and tumor tissue to enhance the efficacy of anticancer drugs. This drug delivery system is designed based on pH-sensitive …

Optimizing Niclosamide For Cancer Therapy: Improving Bioavailability Via Structural Modification And Nanotechnology, Russell Wiggins, Jihoo Woo, Shizue Mito

School of Medicine Publications

Niclosamide, a drug originally used to treat parasitic infections, has shown potential as a possible cancer treatment, but poor absorptive and solubility properties are believed to limit its effectiveness. Researchers are exploring modified structures of the drug along with advanced delivery methods, particularly nanotechnology, to improve niclosamide’s absorption profile and improve its specificity in regard to targeting cancerous cells. These efforts intend to produce more effective tumor-targeting compounds, which can be employed as pharmacological cancer treatment options when appropriate. If successful, these efforts will provide new tools for scientists and doctors, offering a novel approach regarding the treatment of a …

A Pseudo-Surfactant Chemical Permeation Enhancer To Treat Otitis Media Via Sustained Transtympanic Delivery Of Antibiotics, Sophie S. Liu, Joanna M. White, Zhongmou Chao, Ruye Li, Shuxian Wen, Ally Garza, Wenjing Tang, Xiaojing Ma, Pengyu Chen, Susan Daniel

Health & Biomedical Sciences Faculty Publications

Chemical permeation enhancers (CPEs) represent a prevalent and safe strategy to enable non-invasive drug delivery across skin-like biological barriers such as the tympanic membrane (TM). While most existing CPEs interact strongly with the lipid bilayers in the stratum corneum to create defects as diffusion paths, their interactions with the delivery system, such as polymers forming a hydrogel, could compromise gelation, formulation stability, and drug diffusion. To overcome that challenge, we explore the differing interactions present with sodium dodecyl sulfate (SDS), an ionic surfactant and a common CPE, and methyl laurate (ML), a non-ionic counterpart with a similar length alkyl chain. …

Locally Injectable Peptide Hydrogel For Conversion Of Temozolomide And Codelivery Of Sirna In Glioblastoma Multiforme Treatment, Megan Pitz

All Dissertations

Traditional treatment methods for glioblastoma multiforme (GBM) are largely unsuccessful, with a 5-year survival rate of 5.6%. Temozolomide (TMZ), the only chemotherapy FDA-approved for GBM treatment, is a hydrophobic prodrug that is stable in an acidic pH and begins converting to its active form at a physiological pH of 7.4. However, complete conversion of TMZ is observed only at a higher pH, and only about 30% of administered TMZ reaches the central nervous system. Therefore, there is a need for new treatment methods that maximize TMZ delivery to and efficacy at the tumor site. Self-assembling peptides are a unique class …

Utilization Of Semiconductor Nanocrystals In Cancer Diagnose And Treatment, Yasir Q. Almajidi, Ahmed A. Albadri, Mazen M. Jwaid, Yaseen T. Khalaf

Maaen Journal for Medical Sciences

In contemporary times, nanotechnology has emerged as a notably sophisticated technological discipline. It possesses an interdisciplinary and multidisciplinary nature, spanning a wide array of domains including medical science, engineering, biology, physics, materials science, and chemistry. Utilization of nanotechnology offers a significant advantage by enabling precise manipulation and control of properties to effectively address specific challenges in various applications. In the fields of science and biomedicine, there has been extensive exploration into the use of functional nanomaterials, emerging as rapidly advancing and captivating areas of research. Diverse types of nanomaterials, including silicon nanowires, quantum dots, carbon nanotubes, and gold/silver nanoparticles, which …

The Application Of Electrosprayed Minocycline-Loaded Plga Microparticles For The Treatment Of Glioblastoma, Marco Antonio Arriaga, Juan A. Amieva, Jaqueline Quintanilla, Angela C. Jimenez, Julio Ledezma, Silverio A. Lopez, Karen S. Martirosyan, Sue Anne Chew

Health & Biomedical Sciences Faculty Publications

The survival of patients with glioblastoma multiforme (GBM), the most common and invasive form of malignant brain tumors, remains poor despite advances in current treatment methods including surgery, radiotherapy, and chemotherapy. Minocycline is a semi-synthetic tetracycline derivative that has been widely used as an antibiotic and more recently, it has been utilized as an antiangiogenic factor to inhibit tumorigenesis. The objective of this study was to investigate the utilization of electrospraying process to fabricate minocycline-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles with high drug loading and loading efficiency and to evaluate their ability to induce cell toxicity in human glioblastoma (i.e., U87-MG) …

Diffusion Of Ionic Liquid-Modified Polymer Nanoparticles Through Nasal Mucus, Mary Vanlandingham

Honors Theses

Mucosal barriers are a natural defense system for preventing the entry of foreign objects into the body; however, they pose as obstacles for effective drug delivery. Coated polymer nanoparticles have been proven to possess improved rates of diffusion across mucus compared to their uncoated, or bare, counterparts. When choline-based ionic liquids (ILs) are introduced to an aqueous system, their dissociation leads to an increase in solution conductivity which ultimately reduces the viscosity of mucus without significantly affecting its structure. Additionally, ILs are highly tunable, so they work well in a range of pHs and conductivities, making ILs an ideal choice …

Engineered Plga Nanofibers For Drug Delivery, Andrew Mancuso

Dissertations, Theses, and Capstone Projects

Poly-lactic-co-glycolic acid (PLGA) polymers are rapidly gaining momentum as a platform for next-generation drug delivery systems due to their ease and low cost of synthesis, favorable biocompatibility and biodegradability, and lack of toxicity. In particular, the application of drug-loaded PLGA nanofibers directly to a target tissue may represent a promising alternative to traditional routes of drug administration (e.g., oral, injectable) as they offer the potential to greatly improve bioavailability, increase efficacy, and reduce off-target toxicity. Furthermore, the use of such a system may potentially allow for greater flexibility in clinical drug development, by enabling the use of compounds which have …

Self-Assembled Ternary Polypeptide Nanoparticles With Improved Biostability For Drug Delivery In Cancer Therapy, Preye Mike Agbana

Theses and Dissertations--Pharmacy

Cancer remains a real and present threat to global health. In the United States, according to cancer statistics, almost 40% of people will be diagnosed with cancer at some point in their lifetime. Conventional chemotherapy has become the mainstay for cancer treatment option. However, chemotherapeutic agents are plagued with problems such as poor aqueous solubility, chemical degradation, Bio instability, and off-site toxicity due to non-specificity. New drug modalities are needed to tackle the ever-growing burden on cancer. In recent times, the promise of nanotechnology has aided to develop drug delivery vehicles to facilitate the administration of potent chemotherapeutics. Nanoformulations such …

Electromechanical Effects On Micro And Nano Particles Generated From Drug Delivery Devices And Their Implications In Flow And Deposition Efficiency, Mohammed Ali, Mark Miller

Technology Faculty Publications and Presentations

This experimental investigation was undertaken to quantify the electrostatic charge and aerodynamic size distribution of the medicinal drug particles inhaled through an in-vitro mouth-throat (MT) in order to compare the amount of drugs can be delivered to the human lung while mimicking a patient is either sitting or lying. The MT model is a cadaver-based replica cast of human oral-pharyngeal-laryngeal region. Tested drug aerosols were generated by a commercially available metered dose inhaler (MDI). The MT model was placed inside a humidity (95%) and temperature (37^oC) controlled chamber. Its mouth-inlet was positioned horizontally and vertically to simulate sitting …

Influence Of Paclitaxel Nanomedicine On The Pancreatic Tumor Immune Components, Godwin Peasah-Darkwah

Theses and Dissertations

Pancreatic cancer (PanCa) is one of the leading causes of cancer-related mortalities in the U.S due to ineffective therapeutic options. Pancreatic tumors are highly desmoplastic and inhibit efficient uptake of therapeutic payloads. Paclitaxel (PTX) has been tested in PanCa therapy with marginally better clinical outcomes, but remain limited by its poor hemocompatibility, biodistribution and intracellular accumulation in tumor cells. Thus, we synthesized a next generation nanoparticle system for PTX to improve its pharmacokinetics and pharmacodynamics (PKPD) in treating PanCa. We also examined ability of the nano formulation to potentiate gemcitabine (GEM) activity in combating chemoresistance in the pancreatic tumor microenvironment …

The Use Of Silica Nanoparticles For Controlled Drug Delivery Of Nicotine, Jennifer C. Iwenofu

Honors College Theses

Drug molecules can be administered in different ways to the human body. Nanotechnology stands out over other alternatives by delivering drugs to specific locations and reducing reactivity time. In this research, the hydrogen bond between silica nanoparticles and the drug molecule, nicotine, were studied to controllably deliver nicotine by varying pH values.

Targeting Platelets Using Ionic Liquid Coated Nanoparticles, Karen Mun Wong

Honors Theses

Platelets are key players in our body’s inflammatory processes upon activation, which can create physiological problems. Researchers are actively seeking solutions by targeting platelets with therapeutics. The objective of the research in this thesis was to investigate a new and potentially less invasive drug delivery platform using nanoparticles. The topic of the project was to explore the world of ionic liquids and their abilities, when coated on nanoparticles, to bind to platelets. A library of choline carboxylic acid-based ionic liquids (ILs) was first synthesized via salt metathesis while PLGA-based nanoparticles were simultaneously being synthesized via the nanoprecipitation method. The ionic …

Milk Exosomes: Nature's Abundant Nanoplatform For Theranostic Applications, Benilde Adriano, Nycol Cotto, Neeraj Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle vesicles. Exosomes have proven to be excellent nanocarriers for carrying lipids, proteins, mRNAs, non-coding RNAs, and DNAs, and disseminating long-distance intercellular communications in various biological processes. Among various cell-line or biological fluid derived exosomes, milk exosomes are abundant in nature and exhibit many nanocarrier characteristics favorable for theranostic applications. To be an effective delivery carrier for their clinical translation, exosomes must inbuilt loading, release, targeting, and imaging/tracking characteristics. Considering the unmet gaps of milk exosomes in theranostic technology it is essential to focus the …

System For Hiv-1 Treatment To The Brain, Caroline Rose Garcia

Theses and Dissertations

While HIV-1 treatment has been revolutionized by combination antiretroviral therapy in the past two decades, HIV-1 remains persistent in organs that don’t allow easy penetration of anti-HIV drugs (e.g., brain) and cause persistent HIV-1 infections and inflammation. Researchers have turned towards nanotechnology-based drug carriers to combat this challenge, such as nanodiscoidal bicelles (ND) and liposomes. Bicelles entrap the drug in their interior hydrophobic core until metabolized by the body, and the payload can be released at the desired location in a controlled, long-lasting dosage. This study investigated the toxicity and extended-release of an anti-HIV drug-loaded within ND and liposomes for …

New Dithiocarbamates As A Possible Human Serum Albumin Metal Carrier In Drug Delivery Systems And Their Antioxidant And Antiproliferative Activities, Saadi M.D. Al-Nuzal, Azhar M. Haleem, Ken Czerwinski, Salah M. Haleem

Chemistry and Biochemistry Faculty Research

New mono- and bis-dithiocarbamates were prepared from the reaction of organic dihydrazides -NHNH-(C=O)(CH2)x-(C=O)NHNH- (where x = 0, 2, 4) and basic carbon disulfide with varying chain length 10-14 atom as a human serum metal carrier. The products were characterized by various spectrophotometric such as 1H and 13C NMR and elemental analysis. Their antiproliferative activities were examined on two species of the standard strains of the Gram-positive Staphylococcus aureus ATCC 25923 and Gram-negative Escherichia coli ATCC 25922 by following the procedure of broth micro-dilution method (BMM), which was applied at the concentrations: 0.0, 100, 200, and 300 ppm for each compound. …

Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

The cellular delivery of cell-impermeable and water-insoluble molecules remains an ongoing challenge to overcome. Previously, we reported amphipathic cyclic peptides c[WR]₄ and c[WR]₅ consisting of alternate arginine and tryptophan residues as nuclear-targeting molecular transporters. These peptides contain an optimal balance of positive charge and hydrophobicity, which is required for interactions with the phospholipid bilayer to facilitate their application as a drug delivery system. To further optimize them, we synthesized and evaluated a multivalent tricyclic peptide as an efficient molecular transporter. The monomeric cyclic peptide building blocks were synthesized using Fmoc/tBu solid-phase chemistry and cyclization in the …

Drug Delivery In Catheterized Arterial Blood Flow With Atherosclerosis, Saulo Orizaga, Daniel N. Riahi, Jose R. Soto

School of Mathematical & Statistical Sciences Faculty Publications

We study the problem of drug delivery in a catheterized artery in the presence of atherosclerosis. The problem is modeled in the context of a two-phase flow system which consists of red blood cells and blood plasma. The coupled differential equations for fluid (plasma) and particles (red cells) are solved for the relevant quantities in the reasonable limits. The drug delivery problem is modeled with a partial differential equation that is developed in terms of the drug concentration, blood plasma velocity, hematocrit value and the diffusion coefficient of the drug/fluid. A conservative-implicit finite difference scheme is develop in order to …

Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi

Pharmacy Faculty Articles and Research

COVID-19 caused by the SARS-CoV-2 virus is a fast emerging disease with deadly consequences. The pulmonary system and lungs in particular are most prone to damage caused by the SARS-CoV-2 infection, which leaves a destructive footprint in the lung tissue, making it incapable of conducting its respiratory functions and resulting in severe acute respiratory disease and loss of life. There were no drug treatments or vaccines approved for SARS-CoV-2 at the onset of pandemic, necessitating an urgent need to develop effective therapeutics. To this end, the innate RNA interference (RNAi) mechanism can be employed to develop front line therapies against …

Comparative Molecular Transporter Properties Of Cyclic Peptides Containing Tryptophan And Arginine Residues Formed Through Disulfide Cyclization, Eman H. M. Mohammed, Dindyal Mandal, Saghar Mozaffari, Magdy Abdel-Hamied Zahran, Amany Mostafa Osman, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously reported cyclic cell-penetrating peptides [WR]₅ and [WR]₄ as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)_xC] and linear counterparts (C(WR)_xC), where x = 4–5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µM) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast …

Magnetoliposomes In Controlled-Release Drug Delivery Systems, Asahi Tomitaka, Yasushi Takemura, Zaohua Huang, Upal Roy, Madhavan Nair

Health & Biomedical Sciences Faculty Publications

Liposomes, one of the most promising drug delivery carriers, have been extensively studied for the treatment of various diseases and have made their way to the market. Magnetic nanoparticles have been attracting great interest for diagnostic and therapeutic applications due to their unique magnetic properties. An integration of liposomes and magnetic nanoparticles gives great potential to the field of smart drug delivery systems, including magnetically guided drug delivery, image-guided drug delivery, and externally triggered controlled drug release using hyperthermia or alternating magnetic fields. In this review, we discuss the recent development of magnetoliposomes for controlled-release drug delivery systems and their …

Novel Elvitegravir Nanoformulation For Drug Delivery Across The Blood-Brain Barrier To Achieve Hiv-1 Suppression In The Cns Macrophages, Yuqing Gong, Pallabita Chowdhury, Prashanth K.B. Nagesh, Mohammad A. Rahman, Kaining Zhi, Murali M. Yallapu, Santosh Kumar

School of Medicine Publications

The use of antiretroviral therapy (ART) has remarkably decreased the morbidity associated with HIV-1 infection, however, the prevalence of HIV-1-associated neurocognitive disorders (HAND) is still increasing. The blood-brain barrier (BBB) is the major impediment for penetration of antiretroviral drugs, causing therapeutics to reach only suboptimal level to the brain. Conventional antiretroviral drug regimens are not sufficient to improve the treatment outcomes of HAND. In our recent report, we have developed a poloxamer-PLGA nanoformulation loaded with elvitegravir (EVG), a commonly used antiretroviral drug. The nanoformulated EVG is capable of elevating intracellular drug uptake and simultaneously enhance viral suppression in HIV-1-infected macrophages. …

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 …

Iron-Containing Nanoparticles For The Treatment Of Chrionic Biofilm Infections In Cystic Fibrosis, Leisha M. A. Martin

Nanoscience and Microsystems ETDs

Cystic fibrosis (CF) is the most common genetic disease resulting in the morbidity and mortality of Caucasian children and adults worldwide. Due to a genetic mutation resulting in malfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, CF patients produce highly viscous mucus in their respiratory tract. This leads to impairment of the mucociliary clearance of inhaled microbes. In addition to reduced microbial clearance, anoxic environmental conditions in the lungs promote biofilm-mode growth of the pathogenic bacterial species Pseudomonas aeruginosa. Chronic infections of P. aeruginosa begin in early childhood and typically persist until respiratory failure and death result. The …