Chemicals and Drugs Commons^™

Emerging Near-Infrared Targeted Imaging Pharmaceutics For Ovarian Cancer, Angel J. Phillip, Annu Karithara, Subhash Chauhan, Murali Yallapu

School of Medicine Publications

Background: Accurate intraoperative identification of ovarian cancer is challenging, as standard techniques such as visual inspection, palpation, and histopathology often fail to detect microscopic disease. Residual tumor contributes to poor cytoreductive outcomes, high recurrence rates, and chemoresistance. Near-infrared (NIR) imaging using tumor-specific biomarkers has emerged as a promising approach to enhance intraoperative visualization and improve tumor margin delineation. Methods: A focused literature review was conducted using PubMed to identify preclinical and clinical studies evaluating NIR image-guided strategies in ovarian cancer. Studies involving tumor-targeted probes against folate receptor alpha, α3-integrin, mesothelin, and CA125 were included, with emphasis on probe design, delivery, …

Muc13-Associated Molecular Interactome In Pancreatic Cancer, Anupam Dhasmana, Swati Dhasmana, Rajasekhar Baru, Abigail Gomez, Shafiul Haque, Sheema Khan, Murali Yallapu, Subhash Chauhan

School of Medicine Publications

Mucin-13 (MUC13) has emerged as a critical molecular player involved in tumorigenesis, cancer progression, metastasis, and evasion of immune surveillance, including in pancreatic cancer. In this report, we identified MUC13 molecular interactome using an integrated immunoprecipitation and liquid chromatography–mass spectrometry (accession no. of protein data JPST004189) approach combined with systems network biology to determine its plausible functional protein–protein interaction network and associated oncogenic mechanisms. This study reveals a total of 54 key MUC13 interactor proteins (including cyclin-dependent kinase 1, catenin delta 1, Caludin-1, ErbB3-binding protein 1, basic transcription factor 3, tight junction protein 1, etc.). Interestingly, the majority of these …

Prognostic Significance And Interplay Of Circulatory Pcsk-9–Apociii–Chemokine Axis In Type 2 Diabetes And Its Complications: A Pilot Study In North Indian Patients, Mohd Waiz, Sahir S. Alvi, Parvej Ahmad, Bodor Bin Sheeha, Paridhi Puri, Irfan Ahmad, Saheem Ahmad, M. Salman Khan

School of Medicine Publications

Background: Proprotein convertase subtilisin kexin/type-9 (PCSK-9) regulates cholesterol homeostasis through lysosomal degradation of LDL-R and also acts as a pleiotropic mediator of inflammation. Emerging evidence links PCSK-9 to diabetes pathogenesis. Given the genetic diversity and distinct lifestyle of the Indian population, investigating role of PCSK-9 in Indian type-2 diabetes mellitus (T2DM) patients is crucial. Notably, its association with ApoCIII and chemokines such as CXCL2 and MCP-1 remains unexplored.

Results: A total of 187 participants were included: Heathy control (HC; n = 50), T2DM (n = 49), T2DM with nephropathy (T2DM-N; n = 43), and T2DM with dyslipidaemia (T2DM-DL; n = …

Computational Repurposing And Experimental Validation Of Ybx1 Inhibitors In Hepatocellular Carcinoma, Omar Karkoutly, Veerababu Nagati, Subhash Chauhan, Manish Tripathi

School of Medicine Publications

Background/Objectives: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. While early-stage HCC can often be treated with surgical resection, ablation, or liver transplantation, advanced disease typically relies on systemic chemotherapy. Sorafenib is the standard first-line therapy for advanced and unresectable HCC; however, both intrinsic and acquired resistance remain major clinical challenges. The Y-box binding protein-1 (YBX1), a transcription factor implicated in drug resistance across multiple cancers, is highly expressed in HCC and represents a potential therapeutic target. This study aimed to identify novel YBX1 inhibitors using a drug repurposing strategy to overcome sorafenib resistance. Methods: A …

Ubiquitination Of Oncogenic Mutant P53 Via Attenuation Of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth, Mudassier Ahmad, Sahir Sultan Alvi, Haider Ahsan, Carlos Perez, Vivek Kashyap, Neeraj Chauhan, Dae Joon Kim, Nirakar Sahoo, Tamer Oraby, Murali Yallapu, Subhash Chuahan, Bilal Hafeez

School of Medicine Publications

Dysregulated ribosome biogenesis and p53 mutations are known to play oncogenic roles in various cancers, including pancreatic cancer. In this study, we demonstrated the therapeutic potential of BMH-21, a pharmacologic inhibitor of RNA polymerase I, against pancreatic cancer by uncovering a novel molecular mechanism involving RPA194-mediated ubiquitination of mutant p53 without affecting the ubiquitination of wild-type p53. Our key findings are that (i) BMH-21 selectively induces apoptosis and cell growth inhibition of pancreatic cancer cells with no effect on normal human pancreatic ductal epithelial cells; (ii) BMH-21 degrades RPA194; (iii) BMH-21 inhibits recruitment of both RPA194 and RPA135 on rDNA …

Repurposing Of Fda-Approved Drugs Identifies Glipizide As A Potent Hmg-Coa Reductase Inhibitor: A High-Throughput Virtual Screening And Molecular Dynamics Approach For Targeting Hypercholesterolemia, Parvej Ahmad, Eswara N. Hanuma Kumar Ghali, Sahir S. Alvi

School of Medicine Publications

Purpose:

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of mortality worldwide. Several inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-R), the key hepatic cholesterogenic enzyme, are prescribed to treat hypercholesterolemia and ASCVD. Statins, the established HMG-R inhibitors, exhibit promising cholesterol-lowering effects; however, their long-term use has prompted significant concerns, necessitating the search for additional therapeutic candidates with strong HMG-R inhibitory activity. Therefore, this study aims to find potential HMG-R inhibitor/s that may help reduce excess cholesterol levels via targeting HMG-R activity.

Methods: In this study, 1285 FDA-approved small molecules were assessed for their HMG-R inhibitory potential using …

Neuropathic Pain And Related Depression In Mice: The Effect Of A Terpene And A Minor Cannabinoid In Combination, Jose Rios, Mohammed Alnoud, Mohammad Hussain, Zayd Ayas, Emmanuel Franco, Justin D. Mills, Joshua Nwose, Maria Sophia Malbas, Hiram L. Garcia, Manish Kumar Tripathi, Khalid Benamar

School of Medicine Publications

Background/Objectives: Neuropathic pain is one of the most severe types of chronic pain. Although it is difficult to manage, it often co-occurs with depression. Yet, no medication addresses the neuropathic pain and depression comorbidity. Therefore, developing integrated treatment strategies that address both pain and depression is a major public health priority and an unmet need affecting millions. Methods: In this study, we investigated the effect of combining a terpene, Beta-Caryophyllene (BCP), and cannabidiol (CBD) on neuropathic pain and associated depression. We employed a chronic constriction injury (CCI) neuropathic pain model and a series of behavioral tests to evaluate …

Cannabidiol And Beta-Caryophyllene: Chronic Inflammatory Pain, Mohammed Alnoud, Mohammad Hussain, Jose Rios, Emmanuel Franco, Justin D. Mills, Joshua Nwose, Maria Sophia Malbas, Hiram L. Garcia, Sophia Leslie, Manish Tripathi, Khalid Benamar

School of Medicine Publications

While chronic pain is challenging to manage, it always co-exists with depression. Currently, chronic pain and depression are usually treated separately with distinct approaches, yet effectiveness remains elusive. Consequently, the development of integrated therapeutic strategies for pain while addressing depression is a high public health priority and unmet need that affects millions of people. This study aims to determine if the combination of the two phytocannabinoids Beta-Caryophyllene (BCP) and cannabidiol (CBD) is effective for chronic pain while simultaneously showing antidepressant effects. We used a chronic inflammatory pain model (Complete Freund's Adjuvant, CFA) and a battery of pain and depression-like behavior …

Editorial: Endocrine Imbalances Of Mineral Ions And Vitamins In Chronic Disease Pathogenesis, Mor-Li Hartman, Hosam G. Abdelhady, Mohammed S. Razzaque

School of Medicine Publications

No abstract provided.

Statin Effects On The Lipidome: Predicting Statin Usage And Implications For Cardiovascular Risk Prediction, Changyu Yi, Kevin Huynh, Yvette Schooneveldt, Gavriel Olshansky, Amy Liang, Tingting Wang, Habtamu B. Beyene, Aleksandar Dakic, Joanne E. Curran, John Blangero

School of Medicine Publications

Statin therapy is a highly successful and cost-effective strategy for the prevention and treatment of cardiovascular diseases (CVD). Adjusting for statin usage is crucial when exploring the association of the lipidome with CVD to avoid erroneous conclusions. However, practical challenges arise in real-world scenarios due to the frequent absence of statin usage information. To address this limitation, we demonstrate that statin usage can be accurately predicted using lipidomic data. Using three large population datasets and a longitudinal clinical study, we show that lipidomic-based statin prediction models exhibit high prediction accuracy in external validation. Furthermore, we introduce a re-weighted model, designed …

Unveiling The Potential Of Urolithin A In Cancer Therapy: Mechanistic Insights To Future Perspectives Of Nanomedicine, Vinita Karumuru, Anupam Dhasmana, Narsimha Mamidi, Subhash Chauhan, Murali Yallapu

School of Medicine Publications

Cancer remains a leading global health challenge, with high mortality rates persisting despite significant advancements in therapeutic interventions. Major obstacles, including systemic toxicity, therapy resistance, metastasis, and relapses, emphasize the urgent need for safer, more effective, and readily accessible treatment strategies. Among emerging alternatives, natural bioactive compounds have gained considerable attention because of their diverse therapeutic potential and lower toxicity profiles. Urolithin A (UA), a metabolite derived from ellagic acid through gut microbiota metabolism, has emerged as a compelling anticancer agent. UA has multiple mechanisms of action, including the regulation of autophagy, enhancement of mitochondrial function, and inhibition of tumor …

Small-Molecule Mitotic Inhibitors As Anticancer Agents: Discovery, Classification, Mechanisms Of Action, And Clinical Trials, Yazmin Salinas, Subhash Chauhan, Debasish Bandyopadhyay

School of Medicine Publications

Despite decades of research, cancer continues to be a disease of great concern to millions of people around the world. It has been responsible for a total of 609,820 deaths in the U.S. alone in 2023. Over the years, many drugs have been developed to remove or reduce the disease’s impact, all with varying mechanisms of action and side effects. One class of these drugs is small-molecule mitotic inhibitors. These drugs inhibit cancer cell mitosis or self-replication, impeding cell proliferation and eventually leading to cell death. In this paper, small-molecule mitotic inhibitors are discussed and classified through their discovery, underlying …

Efficacy Of Glucagon-Like Peptide-1 Receptor Agonists For Prevention Of Stroke Among Patients With And Without Diabetes: A Meta-Analysis With The Select And Flow Trails, Asmita Gera, Fakhar Latif, Vamsikalayan Borra, Sidra Naz, Vivek Mittal, Fathima Shehnaz Ayoobkhan, Tushar Kumar, Zarghoona Wajid, Novonil Deb, Tanisha Prasad

School of Medicine Publications

Background

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a reduction in major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). However, its efficacy on cerebrovascular events is yet to be well established among diabetic and non diabetic patients.

Objective

We sought to evaluate the efficacy of GLP-1 RAs on stroke risk among its different types in patients with and without Diabetes.

Methods

We performed a systematic literature search on PubMed, EMBASE, and ClinicalTrials.gov for relevant randomized controlled trials (RCTs) from inspection until 15th July 2024, without any language restrictions. Odds ratios (OR) and 95 % …

Relevance Of Cellular Homeostasis-Related Gene Expression Signatures In Distinct Molecular Subtypes Of Breast Cancer, Sharda P. Singh, Chathurika S. Dhanasekara, Michael W. Melkus, Chhanda Bose, Sonia Y. Khan, Flavia Sardela De Miranda, Maria F. Mahecha, Prrishti J. Gukhool, Sahil S. Tonk, Se-Ran Jun

School of Medicine Publications

Background: Breast cancer is a complex and heterogeneous disease characterized by distinct molecular subtypes with varying prognoses and treatment responses. Multiple factors influence breast cancer outcomes including tumor biology, patient characteristics, and treatment modalities. Demographic factors such as age, race/ethnicity, menopausal status, and body mass index have been correlated with variations in incidence, mortality, and survival rates. Over the past decade, comprehensive genomic profiling has been widely used to identify molecular biomarkers and signatures to develop novel therapeutic strategies for patients. For instance, the FLEX registry (NCT03053193) enrolled stage I-III breast cancer patients across 90 institutions in the …

Small Molecule B-Raf Inhibitors As Anti-Cancer Therapeutics: Advances In Discovery, Development, And Mechanistic Insights, Yamile Abuchard Anaya, Ricardo Pequeno Bracho, Subhash Chauhan, Manish K. Tripathi, Debasish Bandyopadhyay

School of Medicine Publications

B-RAF is a serine/threonine kinase that plays a crucial role in the MAPK signaling pathway, regulating cell proliferation and survival. Mutations in B-RAF, particularly V600E, are associated with several malignancies, including melanoma, colorectal cancer, and non-small cell lung cancer, making it a key therapeutic target. The development of B-RAF inhibitors, such as Vemurafenib, Dabrafenib, and second-generation inhibitors like Encorafenib, has led to significant advancements in targeted cancer therapy. However, acquired resistance, driven by MAPK pathway reactivation, RAF dimerization, and alternative signaling pathways, remains a major challenge. This review explores the molecular mechanisms of B-RAF inhibitors, their therapeutic efficacy, and resistance …

Lipid-Based Niclosamide Delivery: Comparative Efficacy, Bioavailability, And Potential As A Cancer Drug, Jihoo Woo, Russel Wiggins, Shizue Mito

School of Medicine Publications

Niclosamide, an FDA-approved anti-parasitic drug, has demonstrated significant potential as a repurposed anti-cancer agent due to its ability to interfere with multiple oncogenic pathways. However, its clinical application has been hindered by poor solubility and bioavailability. Lipid-based nanocarrier systems such as liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid nanoemulsions (LNE), along with lipid prodrugs, have successfully been employed by researchers to overcome these limitations and improve niclosamide’s pharmacokinetic profile. Lipids are the core organic compounds which serve as the foundation of these advanced drug delivery methods and in turn play a critical role in enhancing niclosamide’s …

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 …

Inulin-Based Formulations As An Emerging Therapeutic Strategy For Cancer: A Comprehensive Review, Eswara Naga H K Ghali, Pranav, Subhash Chauhan, Murali M. Yallapu

School of Medicine Publications

Highlights

• Inulin is a naturally occurring prebiotic fiber with therapeutic roles.

• Inulin can act as an excellent carrier for drug delivery in cancer therapy.

• Inulin exhibits an improved therapeutic efficacy in its combination treatments.

• Inulin interventions activate phagocytosis and the TLR4 signaling pathway.

Abstract

Cancer stands as the second leading cause of death in the United States (US). Most chemotherapeutic agents exhibit severe adverse effects that are attributed to exposure of drugs to off-target tissues, posing a significant challenge in cancer therapy management. In recent years, inulin, a naturally occurring prebiotic fiber has gained substantial attention for its potential in …

Proteomic Profiling Of Extracellular Vesicles Isolated From Plasma And Peritoneal Exudate In Mice Induced By Crotalus Scutulatus Scutulatus Crude Venom And Its Purified Cysteine-Rich Secretory Protein (Css-Crisp), Armando Reyes, Joseph D. Hatcher, Emelyn Salazar, Jacob Galan, Anton Iliuk, Elda E. Sanchez, Montamas Suntravat

School of Medicine Publications

Increased vascular permeability is a frequent outcome of viperid snakebite envenomation, leading to local and systemic complications. We reported that snake venom cysteine-rich secretory proteins (svCRiSPs) from North American pit vipers increase vascular permeability both in vitro and in vivo. They also induce acute activation of several adhesion and signaling molecules that may play a critical role in the pathophysiology of snakebites. Extracellular vesicles (EVs) have gained interest for their diverse functions in intercellular communication, regulating cellular processes, blood-endothelium interactions, vascular permeability, and immune modulation. They also hold potential as valuable biomarkers for diagnosing, predicting, and monitoring therapeutic responses in …

Glutathione-Responsive Tannic Acid-Assisted Fret Nanomedicine For Cancer Therapy, Partha Laskar, Anupam Dhasmana, Sudhir Kotnala, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan

School of Medicine Publications

In cancer combination therapy, a multimodal delivery vector is used to improve the bioavailability of multiple anti-cancer hydrophobic drugs. Further, targeted delivery of therapeutics along with simultaneous monitoring of the drug release at the tumor site without normal organ toxicity is an emerging and effective strategy for cancer treatment. However, the lack of a smart nano-delivery system limits the application of this therapeutic strategy. To overcome this issue, a PEGylated dual drug, conjugated amphiphilic polymer (CPT-S-S-PEG-CUR), has been successfully synthesized by conjugating two hydrophobic fluorescent anti-cancer drugs, curcumin (CUR) and camptothecin (CPT), through an ester and a redox-sensitive disulfide (-S-S-) …

Xylazine In The Opioid Epidemic: A Systematic Review Of Case Reports And Clinical Implications, Shahana Ayub, Shanli Parnia, Karuna Poddar, Anil K. Bachu, Amanda Sullivan, Ali M. Khan, Saeed Ahmed, Lakshit Jain

School of Medicine Publications

Introduction and objectives: The opioid overdose epidemic is exacerbated by the emergence of Xylazine as an illicit drug adulterant. Xylazine, a veterinary sedative, can potentiate opioid effects while also causing toxic and potentially fatal side effects. This systematic review aims to assess the impact of Xylazine use and overdoses within the opioid epidemic context.

Method: A systematic search was conducted following PRISMA guidelines to identify relevant case reports, and case series related to Xylazine use. A comprehensive literature search included databases like Web of Science, PubMed, Embase, and Google Scholar, utilizing keywords and Medical Subject Headings (MeSH) terms related to …

Multidrug Resistance In Cancer: Understanding Molecular Mechanisms, Immunoprevention And Therapeutic Approaches, Talha Bin Emran, Asif Shahriar, Aar Rafi Mahmud, Tanjilur Rahman, Mehedy Hasan Abir, Mohd Faijanur-Rob Siddiquee, Hossain Ahmed, Nova Rahman, Firzan Nainu, Elly Wahyudin

School of Medicine Publications

Cancer is one of the leading causes of death worldwide. Several treatments are available for cancer treatment, but many treatment methods are ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions against cancer. This review describes the known MDR mechanisms in cancer cells and discusses ongoing laboratory approaches and novel therapeutic strategies that aim to inhibit, circumvent, or reverse MDR development in various cancer types. In this review, we discuss both intrinsic and acquired drug resistance, in addition to highlighting hypoxia- and autophagy-mediated drug resistance mechanisms. Several factors, including individual genetic differences, such as …

Steviol Represses Glucose Metabolism And Translation Initiation In Pancreatic Cancer Cells, Sonam Kumari, Mohammed Sikander, Shabnam Malik, Manish Tripathi, Bilal B. Hafeez, Murali M. Yallapu, Subhash C. Chauhan, Sheema Khan, Meena Jaggi

School of Medicine Publications

Pancreatic cancer has the worst prognosis and lowest survival rate among all cancers. Pancreatic cancer cells are highly metabolically active and typically reprogrammed for aberrant glucose metabolism; thus they respond poorly to therapeutic modalities. It is highly imperative to understand mechanisms that are responsible for high glucose metabolism and identify natural/synthetic agents that can repress glucose metabolic machinery in pancreatic cancer cells, to improve the therapeutic outcomes/management of pancreatic cancer patients. We have identified a glycoside, steviol that effectively represses glucose consumption in pancreatic cancer cells via the inhibition of the translation initiation machinery of the molecular components. Herein, we …

Bay Leaf Extract‐Based Near‐Infrared Fluorescent Probe For Tissue And Cellular Imaging, Benilde Adriano, Nycol Cotto, Neeraj Chauhan, Vinitha Karumuru, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

The development of fluorescence dyes for near‐infrared (NIR) fluorescence imaging has been a significant interest for deep tissue imaging. Among many imaging fluoroprobes, indocyanine green (ICG) and its analogues have been used in oncology and other medical applications. However, these imaging agents still experience poor imaging capabilities due to low tumor targetability, photostability, and sensitivity in the biological milieu. Thus, developing a biocompatible NIR imaging dye from natural resources holds the potential of facilitating cancer cell/tissue imaging. Chlorophyll (Chl) has been demonstrated to be a potential candidate for imaging purposes due to its natural NIR absorption qualities and its wide …

Bioactive Nanotherapeutic Trends To Combat Triple Negative Breast Cancer, Pallabita Chowdhury, Upasana Ghosh, Kamalika Samanta, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

The management of aggressive breast cancer, particularly, triple negative breast cancer (TNBC) remains a formidable challenge, despite treatment advancement. Although newer therapies such as atezolizumab, olaparib, and sacituzumab can tackle the breast cancer prognosis and/or progression, but achieved limited survival benefit(s). The current research efforts are aimed to develop and implement strategies for improved bioavailability, targetability, reduce systemic toxicity, and enhance therapeutic outcome of FDA-approved treatment regimen. This review presents various nanoparticle technology mediated delivery of chemotherapeutic agent(s) for breast cancer treatment. This article also documents novel strategies to employ cellular and cell membrane cloaked (biomimetic) nanoparticles for effective clinical …

Emergence Of Cationic Polyamine Dendrimersomes: Design, Stimuli Sensitivity And Potential Biomedical Applications, Partha Laskar, Christine Dufès

School of Medicine Publications

For decades, self-assembled lipid vesicles have been widely used in clinics as nanoscale delivery systems for various biomedical applications, including treatment of various diseases. Due to their core–shell architecture and versatile nature, they have been successfully used as carriers for the delivery of a wide range of therapeutic cargos, including drugs and nucleic acids, in cancer treatment. Recently, surface-modified polyamine dendrimer-based vesicles, or dendrimersomes, have emerged as promising alternatives to lipid vesicles for various biomedical applications, due to their ease of synthesis, non-immunogenicity, stability in circulation and lower size polydispersity. This mini-review provides an overview of the recent advances resulting …

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 …

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 …

Bioactive Nanotherapeutic Trends To Combat Triple Negative Breast Cancer, Pallabita Chowdhury, Upasana Ghosh, Kamalika Samanta, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

The management of aggressive breast cancer, particularly, triple negative breast cancer (TNBC) remains a formidable challenge, despite treatment advancement. Although newer therapies such as atezolizumab, olaparib, and sacituzumab can tackle the breast cancer prognosis and/or progression, but achieved limited survival benefit(s). The current research efforts are aimed to develop and implement strategies for improved bioavailability, targetability, reduce systemic toxicity, and enhance therapeutic outcome of FDA-approved treatment regimen. This review presents various nanoparticle technology mediated delivery of chemotherapeutic agent(s) for breast cancer treatment. This article also documents novel strategies to employ cellular and cell membrane cloaked (biomimetic) nanoparticles for effective clinical …

Starting Antihypertensive Drug Treatment With Combination Therapy: Controversies In Hypertension - Con Side Of The Argument, Zhen-Yu Zhang, Yu-Ling Yu, Kei Asayama, Tine W. Hansen, Gladys E. Maestre, Jan A. Staessen

School of Medicine Publications

The 2018 European Society of Cardiology/European Society of Hypertension1 and the 2020 International Society of Hypertension2 guidelines for the management of hypertension proposed that initial combination therapy with 2 antihypertensive agents in a single-pill combination (SPC) is preferred in most patients in need of blood pressure (BP) lowering treatment and should replace the long-standing concept of starting treatment with a single agent, rotating through antihypertensive drug classes, and next moving towards combining drug classes. By moving SPCs forward as the initial BP-lowering strategy, the European1 and International2 Societies of Hypertension Guideline Committees overlooked several principles in …