Formulation And Characterization Of Biologics – From Sirna To Monoclonal Antibodies, Chinmay M. Jogdeo

Theses & Dissertations

Biologics are a rapidly growing class of therapeutics, encompassing a wide range of modalities, with gene therapy products and monoclonal antibodies (mAbs) constituting the majority. Proper formulation and characterization of these complex therapeutics is crucial to ensure their safety and therapeutic efficacy.

This dissertation focuses on two main areas: the development of a novel renal-targeted siRNA delivery system and the assessment of structural and conformational stability of mAbs in a simulated subcutaneous (SC) environment.

The first part of this dissertation presents the synthesis and characterization of a novel renal-targeted polymer for selective siRNA delivery to injured kidneys. Inulin was modified …

Tension Recordings From Primary Bronchi In Acta2-Gcamp8.1-Mvermilion Transgenic Mice, Qais Khalaf, Srijit Ghosh, Keith Thornbury

SURE Journal: Science Undergraduate Research Experience Journal

Contractions in smooth muscle cells are initiated by elevation of cytosolic Ca²⁺. It is of interest to measure Ca²⁺ signals in these cells. Transgenic Acta2-GCaMP8.1-mVermilion (GCaMP) mice express a genetically encoded intracellular fluorescent Ca²⁺ indicator in smooth muscle cells, have been developed to facilitate the study of Ca²⁺. However, there is a concern that the GCaMP Ca²⁺ indicator might buffer Ca²⁺ and interfere with the signals it is designed to measure. Therefore, the aim of this study was to compare tension responses in GCaMP and wild type (WT) mice to determine if …

Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

Computational Logp Calculations And Determination Of Lipophilicity Values Of Fluorinated Morphine Derivatives, Mirabella Romano, Allison Vu, Emily Chen

Student Scholar Symposium Abstracts and Posters

The addictive effect of opioids impacted 60 million people globally in 2023. This opioid crisis necessitates the development of opioid derivatives that maintain analgesic efficacy while minimizing addictive effects from opioid use. The present work focuses on morphine, a commonly prescribed opioid with high affinity to the mu-opioid receptor (MOR). Morphine binds non-selectively within both healthy and inflamed tissue. By modifying morphine’s structure through fluorination to counteract its non-selective binding, the drug’s pharmacological ability to provide effective pain relief comes with a lower risk of addiction. Specifically, the addition of fluorine to differing beta positions of the main binding site …

Anti-Inflammatory Potential Of Black Cumin Seed Oil And Its Nanoemulsion Formulation Against Lipopolysaccharide-Induced Liver Injury In Mice, Shady Swidan, Hesham Hafez, Rehab Hosni, Hatem Amin

Pharmacy

Original Article

Anti-inflammatory potential of black cumin seed oil and its nanoemulsion formulation against lipopolysaccharide-induced liver injury in mice

Haffez, Hesham^1,2,✉; Hosni, Rehab³; Swidan, Shady A.⁴; Amin, Hatem K.^1,5

Author Information

¹Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, 11795, Cairo, Egypt

²Center of Scientific Excellence “Helwan Structural Biology Research”, Helwan University, Helwan, 11795, Cairo, Egypt

³El Sisi Comprehensive Clinic, General Authority for Health Insurance-Giza, Haram, 12556, Giza, Egypt

⁴Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, El-Sherouk, 11837, Cairo, …

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina L Mayer, Nobuyuki Matoba

The Cardinal Edge

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. Upon binding to cancer cells, AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill the cancer cells. Previous work has shown that AvFc effectively induces ADCC activity …

Evaluating Tirzepatide's Therapeutic Potential In Mitigating Obesity-Associated Comorbidities, Zaneh Kahook, Talaya Jones, Carina Bryan, Mayur Parmar

HCA-NSU MD Research Day

Objective: The study aims to explore the therapeutic potential of dual GIP/GLP-1 agonist tirzepatide in managing obesity and its associated manifestations, including obstructive sleep apnea (OSA), hidradenitis suppurativa (HS), and obesity-associated cancer (OAC) risks. Background: OSA and HS are the associated comorbidities noted in persons with obesity. Obesity has been associated with an increased risk of cancers, such as breast cancer. Reducing obesity could improve these conditions. Tirzepatide has demonstrated efficacy in reducing body weight, but its benefits in obesity-related conditions and cancer risk need further investigation. Methods: Data was synthesized from peer-reviewed literature on tirzepatide. Additional sources were identified …

Synthesis And Evaluation Of Cyclic Peptide-Dasatinib Conjugates As Anti-Melanoma Agents, Shaban Darwish, Dorna Davani-Davari, Shirley Tong, Rakesh Kumar Tiwari, Sun Yang, Keykavous Parang

Pharmacy Faculty Articles and Research

Herein, we synthesized two amphiphilic cyclic peptides, incorporating tryptophan and arginine residues, linked to dasatinib via a Cathepsin B-sensitive tetrapeptide (Gly-Phe-Leu-Gly). To mitigate steric hindrance and optimize drug release, we integrated two different linkers, succinate and glutarate, between the drug and peptide. The synthesis involved solid-phase techniques for the assembly of the peptide, followed by the coupling of the peptide on-resin with the linker, mild cleavage, and solution-phase cyclization. Conjugation of the peptide-attached linker with dasatinib was conducted in the presence of N-methylmorpholine and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), generating the novel prodrugs. The synthesized compounds were characterized by high-resolution mass …

Harnessing The Potential Of Several Local Indonesian Tuber-Derived Starches As Pharmaceutical Excipients, Ronald Horison, Silvia Surini

Pharmaceutical Sciences and Research

Starch is one of the widely required excipients in pharmaceutical dosage forms manufacturing. Indonesia’s rich biodiversity, encompassing tubers like arrowroot, taro beneng, porang, ganyong and yams, harbours the potential for novel starch excipient sources. These tubers provide starch variations with distinct functional properties influenced by the natural starch granules’ properties and amylose-amylopectin ratio. Previous research utilizing natural and modified starches from these tubers has demonstrated their potential in pharmaceutical formulation. These starch tubers have been studied and provided promising results in tablet formulation and film development. Additionally, they could be involved in developing more advanced dosage forms, such as starch …

A Review Of 3d Printing Technology In Drug Design Applications, Hasanain Shakir Mahmood, Jinan M. Al-Mousawy, Jamal Ali Ashoor, Ashti M.H. Saeed, Alaa Abdul Razzaq Al-Nuaimi, Pegah Khosravian

Maaen Journal for Medical Sciences

Sustainable technologies such as Additive manufacturing or three-dimensional printing (3D printing) have resulted in drastic changes in a number of industries including healthcare and pharmaceuticals. The current review focuses on the achievements accomplished on the effectiveness of three-dimensional printing in the field of drug designing and development. This technology is very precise and can be customized and that gives a way of developing complicated drug delivery systems and individualized medications. Promising areas of focus are the development of particular formulations of medicinal preparations, identification of new approaches to the drug release and potential creation of specific drug production for specific …

Hepatic Targets To Control Blood Glucose And Potentially Aid In The Treatment Of Diabetes, Rena A. Velissarios

PANDION: The Osprey Journal of Research and Ideas

Maintaining glucose homeostasis is extremely important to remain in good health and prevent disease. This homeostasis is achieved via the regulation of hepatic metabolic pathways like gluconeogenesis and glycogenesis by insulin, which is expressed during high blood glucose. Insulin is responsible for facilitating the uptake of glucose into other tissues from the blood, as well as signaling whether to stimulate or slow glucose metabolism in the liver. Hyperglycemia is one of the main effects of diabetes, a disease characterized by the body’s inability to produce or respond to insulin. Without insulin, hepatic glucose output continues and blood glucose accumulates, causing …

The Impact Of Pdcd4, A Translation Inhibitor, On Drug Resistance, Qing Wang, Hsin-Sheng Yang

Markey Cancer Center Faculty Publications

Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, growing evidence suggests that Pdcd4 enhances the chemosensitivity of several anticancer drugs. To date, numerous translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may improve chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.

Molecular Targets For Breast Cancer Therapy, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

"Breast cancer is by far the most common cancer in women, and for a while, it surpassed lung cancer as the most diagnosed cancer, regardless of gender, in 2020 [1]. Chemotherapy and hormone therapy are still the first line of treatment, despite extensive research in molecularly targeted drugs. Therefore, triple negative breast cancer (TNBC) is still known as the most challenging type for treatment due to the limited identified targets. Inherent and acquired resistance are still major hurdles in breast cancer therapy, which further highlights the importance of identifying new molecular targets in this battle. The inherent resistance of unresponsive …

Cellular Uptake And Computational Analysis Of [131i]-Xanthine And [131i]-Hypoxanthine In Human Prostate Cancer Cell Line (Lncap), Hendris Wongso, Isa Mahendra, Yanuar Setiadi, Badra Sanditya Rattyananda, Asep Rizaludin, Ni Made Yuktikamura Galih Pranisuari, Crhisterra Ellen Kusumaningrum

Makara Journal of Science

Potent radiolabelled compounds eligible for therapy of prostate cancer need to be developed. Hence, we developed two candidate therapeutic agents bearing the iodine-131 (¹³¹I) radionuclide, namely, [¹³¹I]-xanthine (3,7-dihydropurine-2,6-dione) and [¹³¹I]-hypoxanthine (1,9-dihydro-6H-purin-6-one). The radiolabelled compounds were subjected to a cellular uptake study, which was accomplished by incubating [¹³¹I]-xanthine and [¹³¹I]-hypoxanthine with the human prostate cancer cell line (LNCaP) for 5, 15, 30, 60, and 90 min. Results showed that the accumulation of both [¹³¹I]-xanthine and [¹³¹I]-hypoxanthine in prostate cancer cells was significantly higher than the …

Targeting Ribosome Biogenesis Is A Novel Approach For The Management Of Pancreatic Cancer, Mudassier Ahmad, Haider Ahsan, Carlos Perez, Muhammad Bangash, Andrew Massey, Emmanuel Anning, Manish Tripathi, Dae Kim, Subhash C. Chauhan, Bilal Bin Hafeez

Research Colloquium

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related deaths in the United States with limited therapeutic options available. Gemcitabine, a deoxycytidine nucleoside analog is currently considered the most effective therapy for PanCa. However, it shows only a marginal survival benefit of six months. Aberrant ribosome biogenesis occurs in most tumor types. We observed that PanCa cells are addicted to ribosome biogenesis, which supports their highly aggressive metastatic phenotypes. Thus, strategically targeting ribosome biogenesis process could be one of the ideal strategies for the prevention and treatment of PanCa. In this study, we elucidated the molecular mechanisms of POLR1A …

Taste Masked Of Eplerenone Using Egg Box Method, Asmaa Mohammed Rashid

Maaen Journal for Medical Sciences

Eplerenone is a selective mineralocorticoid receptor antagonist employed to manage hypertension, central serous retinopathy, and chronic heart failure. It has a highly bitter taste, which reduces patient compliance with the drug.

The aim of this study was masking the very bitter taste of the eplerenone to improve patient compliance especially for geriatric patient.

The medication was encapsulated utilizing the ionic gelation process, in which a 1% w/w sodium alginate solution was utilized to form egg box structures.Two different concentrations of CaCl2 (0.5.1%w/v) were used as cross-linkers, and different drug: polymer ratios were tested. The formulas were evaluated based on their …

Incorporating Solvation Thermodynamic Mapping In Computer-Aided Drug Design, Yeonji Ji

Dissertations, Theses, and Capstone Projects

Advancements in computational techniques have revolutionized structure-based drug design, substantially improving the efficiency and effectiveness of the drug discovery process by reducing time, costs, and labor requirements. These advancements include various methods, such as investigating small molecule ligands binding to proteins, exploring alternative protein conformations, and solvation mapping on the protein surfaces. Among these methods, understanding the correlation between protein-ligand binding and the role of solvation is important.

A fundamental concept in protein-ligand binding is shape and electrostatic complementarity, which is complicated by the inherent flexibility of proteins. In the absence of small molecule ligands, proteins are complementary to surface …

Challenges And Future Perspective Of Gastroretentive Mucoadhesive Dosage Forms, Rayhan Akbar, Heri Setiawan, Baitha Palanggatan Maggadani, Raditya Iswandana, Kurnia Sari Setio Putri

Pharmaceutical Sciences and Research

Gastroretentive Mucoadhesive Dosage Form (GMDF) is one type of Gastroretentive Drug Delivery System (GRDDS) technology designed to exploit the adhesiveness of dosage forms in the gastric mucosa. This aims to increase drug residence time, enhance drug solubility and absorption, and ultimately improve drug bioavailability and therapeutic effect. Various studies have explored the use of different polymers to develop GMDF systems and dosage forms. However, despite extensive research in this field, there are still limited GMDF products approved by the US FDA and INA FDA. Therefore, this review addresses the challenges in developing GMDF, its current state, and potential future opportunities. …

Application Of Pvp Va 64 And Poloxamer 188/407 In Solid Dispersion Technology For Improving Solubility Of Valsartan, Sulastari Cahyani, Teuku Nanda Saifullah Sulaiman, Marlyn Dian Laksitorini

Pharmaceutical Sciences and Research

Valsartan, Biopharmaceutical Classification System (BCS) class II drug, exhibits pH-dependent solubility in the gastrointestinal tract, which increases at pH levels above 5. Its low solubility results in a bioavailability of only 23%, necessitating efforts to enhance it. This study aims to improve the solubility of valsartan using a solid dispersion system. Polyvinylpyrrolidone/vinyl acetate 64 (PVP VA 64), a hydrophilic polymer, was incorporated to inhibit the recrystallization of valsartan, while poloxamer 188 and poloxamer 407, used as surfactants, aimed to enhance valsartan’s solubility and intrinsic dissolution rate. Valsartan solid dispersions were prepared using the spray drying method, and the optimal formulation …