Pharmaceutics and Drug Design Commons^™

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. …

Biosynthesis Of Agnps Mediated By Equisetum Debile Roxb. Herb Water Extract And Its Potency As An Antioxidant, Yuni Retnaningtyas, Alviani Dwi Karmilasari, Endah Puspitasari

Pharmaceutical Sciences and Research

Silver nanoparticles (AgNPs) are metal nanoparticles currently under development. AgNPs are recognized for their remarkable stability, low reactivity, and advantageous biological properties, including antioxidant activity. Phenolic compounds derived from the Equisetum debile Roxb. (Ed-R) herb have the potential to be explored as bio-reduction and capping agents in the synthesis of silver nanoparticles. The primary objective of this study is to synthesize AgNPs using a water extract from Ed-R herb and to assess their antioxidant activity. The optimal composition for the biosynthesis of AgNPs comprises 10% Ed-R water extract, 8.0 mM AgNO₃, and deionized water in a ratio of …

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 …

Cell-Based Medicinal Products: Progress And Perspectives, Lijian Hui, Xiang Yuan, Jingqi Wu

Bulletin of Chinese Academy of Sciences (Chinese Version)

Cell-based medicinal products are a breakthrough that has been proven to treat previously incurable diseases, making them a topic of global interest. This review delves into the current state and progress of cell therapy, highlighting the remarkable therapeutic effects of various types of cell-based medicinal products. We specifically explore the potential development of cell-based medicinal products in China, focusing on promoting clinical translation and commercialization. We propose necessary actions to achieve these goals, such as fostering cutting-edge basic research, innovative therapeutic approaches, scalable manufacturing processes, and policy changes.

Injectable Formulations For Localized Delivery Of Immunomodulators, Ketki Velankar

Electronic Theses and Dissertations

Dysregulation of immune homeostasis is fundamental to the development of autoimmune disorders. Fibroblastic reticular cells (FRCs) within lymph nodes play crucial roles in forming a microenvironment conducive to immune cell interactions and regulating autoreactive T cells driving autoimmune diseases. Studies have shown the potential of FRCs as a form of personalized cell therapy to correct dysregulated immune responses. Successful translational efforts, however, require the cells to be formulated as injectable suspensions while retaining their native architecture, which is essential for their regulatory functions. The main challenge resides in retaining the native reticular organization of FRCs lost in conventional monolayer cultures …

Uptake Of Extracellular Vesicles Into Brain Endothelial Cells And Development Of Motor Neuron-Derived Extracellular Vesicles For Amyotrophic Lateral Sclerosis, Jhanvi Rajan Jhaveri

Electronic Theses and Dissertations

Extracellular vehicles (EVs) are an emerging class of drug carriers and are primarily reported to be internalized into recipient cells via a combination of endocytic routes such as clathrin-mediated, caveolae-mediated and macropinocytosis pathways. In part one of this thesis, (1) we investigated potential effects of homotypic vs. heterotypic interactions by studying the cellular uptake of homologous EVs (EV donor cells and recipient cells of the same type) vs. heterologous EVs (EV donor cells and recipient cells of different types) and (2) determined the route of EV internalization into low pinocytic/hard-to-deliver cell models such as brain endothelial cells ( …

Delivery Of Mitochondria-Containing Engineered Extracellular Vesicles To The Blood-Brain Barrier For Ischemic Stroke Therapy, Kandarp Dave

Electronic Theses and Dissertations

Ischemic stroke is the second leading cause of death worldwide, and the lack of effective treatment options is an unmet clinical need for stroke survivors. Ischemic stroke-induced oxygen-glucose deprivation (OGD) in the affected brain tissue leads to mitochondrial dysfunction and adenosine triphosphate (ATP) depletion in the brain endothelial cells (BECs) lining the blood-brain barrier (BBB). ATP deprivation in the BECs dysregulates actin cytoskeleton dynamics, resulting in BBB breakdown. Restoration of blood flow (i.e., reperfusion) upon the first-line stroke treatment further leads to BBB breakdown and widens the paracellular spaces between BECs. …

A Third Generation Long-Acting Dimeric Dolutegravir Prodrug Nanoformulation, Bhoomika Suresh Gowda

Theses & Dissertations

Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) widely used as a part of first-line combination antiretroviral therapy. DTG has a high barrier to resistance However, one therapeutic challenge centers on its life-long daily use. Sub-optimal adherence to daily oral pills underscore the need for long-acting formulations. To these ends, our research activities have focused on the development and translation of ultra-long-acting ART. Monomeric ester prodrugs provided initial success in extending the apparent half-life of DTG and other INSTIs. One is the DTG prodrug formulation called NM2DTG. NM2DTG’s significantly extended the parent drug’s apparent half-life [Nature Communications, 3226 (2022)]. …

Pharmacokinetics And Tissue Distribution Of A Lipid-Based Extended-Release Nano-Formulation Of Mo-Oh-Nap Tropolone To Enhance Pulmonary Delivery For The Treatment Of Pulmonary Metastatic Osteosarcoma, Wafaa N. Aldhafiri

Theses & Dissertations

Osteosarcoma is the most common primary bone tumor in children and adolescents. Metastasis is prevalent in 25% of patients, at diagnosis, with the lungs being the most common metastatic site. Pulmonary metastatic osteosarcoma is a significant therapeutic challenge with a 5-year survival rate of ≤30%. Patients with pulmonary metastatic disease at diagnosis receive the same standard of care as patients with local disease, which hasn’t changed over the past 30 years. The treatment and prevention of pulmonary metastatic osteosarcoma represents a significant critical and unmet need.

MO-OH-Nap tropolone is a novel small molecule with cytotoxic activity across multiple human osteosarcoma …

Advancement In In-Silico Drug Discovery From Virtual Screening Molecular Dockings To De-Novo Drug Design Transformer-Based Generative Ai And Reinforcement Learning, Dony Ang

Computational and Data Sciences (PhD) Dissertations

The field of drug discovery has seen remarkable advancements over the past few decades, transitioning from traditional experimental methods to highly sophisticated computational approaches. One of the pivotal techniques in this evolution is virtual screening, which utilizes molecular docking to predict the interaction between small molecules and target proteins. This method has significantly accelerated the initial stages of drug discovery by enabling the high-throughput screening of large chemical libraries. By simulating the binding affinity and stability of potential drug candidates, virtual screening has become a cornerstone in identifying promising compounds for further development.

A notable application of virtual screening was …

Development Of A Novel Drug Delivery Platform To Treat Hiv-Associated Neurocognitive Disorder, Lina Zhou

Alternative Theses and Dissertations (AETDs)

Despite the significant reduction in HIV prevalence and improvement in life expectancy achieved through the availability of widespread antiretroviral therapy (ART), there remains no definitive cure for HIV. Further, HIV infects the brain as early as eight days after initial peripheral infection leading to neuroHIV and subsequently neuronal damage and cognitive impairment. HIV can enter the brain through several mechanisms, including the migration of infected immune cells (Trojan Horse Mechanism), direct infection of endothelial cells, and cytokine-mediated disruption of the blood-brain barrier (BBB). Consequently, HIV-associated neurocognitive disorder (HAND) remains a significant challenge in the ART era, with an estimated prevalence …

Comments Re: Draft Nih Intramural Research Program Policy: Promoting Equity Through Access Planning, Fred Ledley M.D., Edward Zhou Pharmd., Paula Chaves Da Silva Ph.D.

CISI Publication

We commend the NIH initiative to require that licensees of technologies that enable discovery or development of FDA-approved products arising from the NIH intramural program to include an Access Plan to promote “product affordability, availability, acceptability, and sustainability” and recognition that such protections are essential to ensuring a “return on taxpayers' investment in biomedical research.” Recognizing the complexity of anticipating appropriate terms for products that are in pre-clinical or early clinical development at the time of licensing, we also support the proposal that the Access Plan be submitted in late-stage clinical development, though we argue that …

Tech Note 2024-1 A Novel Framework To Estimate Social And Private Value Created Through Commercialization Of A Pharmaceutical Product, Paula Chaves De Silva, Fred D. Ledley

CISI Publication

This framework posits that the value created by a new medicine is embodied in the total health value (health benefit) provided to those using the products. This value is then distributed between social value and private value by the price paid for the product and how these revenues are expensed for different purposes. In this framework, the social value created includes the residual health value (net price paid) along with the scientific value, jobs creation, and social payments to public sector organizations. The private value created includes shareholder value (change in market capitalization plus cash distributions to shareholders) as well …

Data-Driven Drug Repurposing For Immune System-Related Diseases, Sabyasachi Mohanty

Department of Biochemistry: Dissertations, Theses, and Student Research

In this research, we explore a data-driven approach for drug repurposing to enhance the immunomodulatory effect by integrating pattern-based search and genome-scale metabolic modeling. This research helps to find a solution to the preexisting problems of drug discovery which includes expenses and a high amount of time consumption. By leveraging the pre-existing data of the approved drugs to identify the major metabolic pathway changes, we can find new drugs with similar effects with less off-target effects.

The focus on the immune system modulating drugs is due to the high prevalence of immune system-involved diseases and the growing demand for effective …

Review Of Mpges-1 Inhibitors Based On The Benzoxazole And Its Isostere Scaffold For The Treatment Of Inflammatory Diseases, Abdullah M. Alwagdani

Longitudinal Scholar's Project

The vital role of the prostanoid pathway in inflammation, pain, cancer, Alzheimer’s and many other diseases has attracted the drug discovery community to discover targets for therapeutic development. Although existing non-steroidal anti-inflammatory drugs (NSAIDs) inhibiting cyclooxygenases (COX) are widely used, the side effects of these NSAIDs limit the ling time medication. Microsomal prostaglandin E synthase-1 (mPGES-1) is an attractive target that is overexpressed during inflammations, and it could be a safe alternative to NSAIDs for treating inflammatory diseases.Since the discovery of mPGES-1 in 1997, many inhibitors have been developed since 2001. Only a few compounds were able to make it …

Microencapsulation Of Cosmos Caudatus Kunth Extract Using Sodium Alginate And In Vitro Antioxidant Activity Test, Safina Samara Nur Fadlila, Oktavia Eka Puspita, Zubaidah Ningsih, Anna Safitri

Makara Journal of Science

This study aims to encapsulate Cosmos caudatus K. leaf extract in sodium alginate crosslinked with calcium chloride (CaCl₂) as coating materials through freeze-drying. Antioxidant assays were performed to evaluate the applicability of the microcapsules as antidiabetic medicines. Their characteristics, antioxidant activity, and encapsulation efficiency (EE) were also examined. Results indicated that the concentration of sodium alginate and pH influenced the manufacturing process of the microcapsules. The highest EE was obtained at pH 6 and alginate concentration of 2% (w/v). The IC₅₀ for the antioxidant activity of the microcapsules was 139.96 ± 1.094 μg/mL. Scanning electron microscopy confirmed …

Targeting Trpc3: A Promising Therapeutic Strategy For Alzheimer's Disease, Jiaxing Wang

Alternative Theses and Dissertations (AETDs)

Alzheimer's disease (AD) is a progressive neurological disorder characterized by extracellular β-amyloid (Aβ) plaques and intracellular tau tangles. The calcium (Ca2+) hypothesis of AD proposes that disrupted intracellular Ca2+ regulation underlies AD pathology, contributing to inflammation, oxidative stress, impaired autophagy, neurodegeneration, and cognitive dysfunction. Store-operated Ca2+ entry (SOCE) maintains ER Ca2+ stores, involving transient receptor potential canonical (TRPC) and Orai channels. Specifically, we speculated that dysregulated functions of TRPC3 contribute to the pathogenesis of AD. We believe that targeting TRPC3 with a pharmacologically feasible agent could prove beneficial in halting cognitive decline. We previously reported compound JW-65, a novel, metabolically …

Targeted Drug Delivery: Investigating Protein Corona Behavior, Atharva Markale

Theses

Due to high specificity and less toxicity, nanoparticles have become promising for targeted drug delivery against cancer, although they face challenges when they enter the bloodstream, making their behavior unpredictable. The deposition of proteins on nanoparticles, the protein corona, changes their biosignature, affecting their circulation, drug release potency, targeting ability, and immunogenicity. The continuous exchange of protein layers on a nanoscale is complex to analyze.

Nanoparticle tracking analysis (NTA) is a method to characterize nanoparticles in blood plasma by combining principles of light scattering microscopy and Brownian motion. In this work, time-dependent experiments with plasma were conducted to analyze the …