Chemicals and Drugs Commons^™

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Management Of Hip Fracture Patients On Direct Oral Anticoagulants: A Survey Of Orthopaedic Trauma Surgeons, Systematic Review, And Meta-Analysis, Clay Spitler, Robert Rutz, Nigel Blackwood, Meghan Wally, Joseph Johnson, Peter Krause, Jaimo Ahn, Zuhair Mohammed, Mark Mcclure, Rebecca Billings, Ziqing Yu, Matthew Yeager

School of Medicine Faculty Publications

OBJECTIVES: This systematic review examined the literature regarding management of fracture patients who take direct oral anticoagulant (DOAC) medications, with a focus on delay in surgical treatment, and need for transfusions. In addition, a survey of orthopaedic trauma surgeons was conducted to gain insight on current practices. DATA SOURCES: A review of PubMed, Cochrane, Embase, and Scopus databases was performed from inception through March 2024, including English language publications. STUDY SELECTION: Studies were included if they reported time to surgery and transfusion rates among fracture patents who were taking DOAC medications. Additional data points were collected on an "if-reported" basis, …

Beyond Checkpoint Inhibitors: The Three Generations Of Immunotherapy, John Schaub, Shou-Ching Tang

School of Medicine Faculty Publications

Anti-tumor immunotherapy was rediscovered and rejuvenated in the last two decades with the discovery of CTLA-4, PD-1 and PD-L1 and the roles in inhibiting immune function and tumor evasion of anti-tumor immune response. Following the approval of the first checkpoint inhibitor ipilimumab against CTLA-4 in melanoma in 2011, there has been a rapid development of tumor immunotherapy. Furthermore, additional positive and negative molecules among the T-cell regulatory systems have been identified that that function to fine tune the stimulatory or inhibitory immune cells and modulate their functions (checkpoint modulators). Many strategies are being explored to target macrophages, NK-cells, cytotoxic T-cells, …

Exploring Microrna Pathways And Metformin's Anti-Inflammatory Potential In Osteoarthritis, Quang D La, Benjamin Tangkamolsuk, David F Lo

Rowan-Virtua School of Osteopathic Medicine Departmental Research

No abstract provided.

Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo

Graduate Theses/Dissertations

Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its …

Multi-Modal Neo-Adjuvant Anti-Obesity Medications May Be More Effective Than Medically Supervised Weight Loss Or Glp-1 Therapy Alone In Preparing Bmi ≥ 70 Patients For Metabolic Surgery, Michael Kachmar, Florina Corpodean, Iryna Popiv, Kyle B. Lapenna, Denise M. Danos, Michael W. Cook, Brian A. Saunders, Jean J. Domercant, Vance L. Albaugh, Philip R. Schauer

School of Medicine Faculty Publications

Background/objectives: Optimizing patients with a body mass index (BMI) ≥ 70 kg/m² for metabolic surgery (MS) is challenging. However, pre-operative weight loss may be important for improving the safety of MS for these high-risk patients. Multi-modal anti-obesity medications (mmAOM) may enhance preoperative weight loss compared to non-pharmacologic medically supervised weight loss (NP-MSWL) or glucagon-like peptide-1 receptor agonist monotherapy (Mono-GLP-1) alone. Subjects/methods: This retrospective study analyzed 113 patients with BMI ≥ 70 kg/m² at a single metabolic disease treatment institute. Interventions/methods: Patients were categorized into NP-MSWL (n = 13), Mono-GLP-1 (n = 54), and mmAOM (n = 46) groups. The primary …

Nitrous Oxide Induced Psychosis: A Case Report, Brianne Kimmet, Barbara Gracious

South Atlantic Division GME Research Day 2025

No abstract provided.

Psychedelic Minimalism: The Case Against Music In Psychedelic Therapy Settings, Samir A. Nader

Department of Medicine Faculty Publications

[Introduction: reframing the role of setting] In recent years, renewed attention has been given to the centrality of set and setting in psychedelic-assisted therapy. The Reporting of Setting in Psychedelic Clinical Trials (ReSPCT) guidelines reflect an evolving consensus: therapeutic outcomes are not solely pharmacologically determined but are heavily shaped by both the environment and the psychological state of the participant (2). Within this evolving paradigm, music has assumed a privileged role, framed as a therapeutic constant, typically curated to be emotionally supportive or evocative, and especially emphasized during peak psychedelic states (3). The prevailing assumption is that music facilitates safety, …

Ribosome Hibernation In Mycobacterium Abscessus And Its Effect On Antibiotic Resistance, Ryan Treen

Electronic Theses & Dissertations (2024 - present)

Non-tuberculosis mycobacteria (NTM) represent a diverse repertoire of species, most of which are ubiquitous in the environment. Some NTM species, such as Mycobacterium abscessus, can cause life-threatening infections in people with underlying medical conditions. The clinical incidence of such infections is on the rise, posing an emerging threat to public health. M. abscessus is characterized by intrinsic and acquired antibiotic resistance, complicating treatment strategies. Most chemotherapeutic approaches for M. abscessus infection target the bacterial ribosome, necessitating a better understanding of the physiological processes which confer this resistance. Multiple mycobacterial species respond to zinc-limiting conditions by inducing remodeling and hibernation …

The Complexity And Significance Of Fibroblast Growth Factor (Fgf) Signaling For Fgf-Targeted Cancer Therapies, Anh Nguyen, Caroline Facey, Bruce Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 …

Glucagon-Like Peptide-1 Receptor Agonist Mediated Weight Loss And Diabetes Mellitus Benefits: A Narrative Review, Alan D. Kaye, Nathan Lien, Christopher Vuong, Matthew H. Schmitt, Yusra Soorya, Bushirat A. Abubakar, Luke Muiznieks, Noah Embry, Harish Siddaiah, Adam M. Kaye, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

Obesity and type 2 diabetes mellitus (T2DM) are chronic diseases with increasing prevalence, underscoring the urgent need for effective treatment and management strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as an essential class of drugs for managing both obesity and T2DM, offering additional benefits for cardiovascular and kidney health. GLP-1 RAs work by targeting GLP-1 receptors, mimicking the effects of the natural hormone GLP-1 to regulate blood glucose levels, promote weight loss, and provide potential benefits for cardiovascular health. This narrative review evaluates the mechanisms of action, clinical efficacy, and broader roles of GLP-1 RAs in promoting weight …

Evolving Treatment Strategies For Systemic Lupus Erythematosus In Clinical Practice: A Narrative Review, Alan D. Kaye, Joseph P. Tassin, William C. Upshaw, Chandni R. Patel, Alison M. Hawkins, Caroline R. Burroughs, Kristin Nicole Bembenick, Chizoba N. Mosieri, Shahab Ahmadzadeh, Adam M. Kaye, Sahar Shekoohi, Giustino Varrassi

School of Dentistry Faculty Publications

Systemic lupus erythematosus (SLE) is an autoimmune disease that more commonly affects African American people, although it is seen in people of all racial backgrounds. This condition is characterized by a dysregulated immune response resulting in widespread inflammation. Clinical manifestations caused by this inflammation include arthritis, anemia, cutaneous rashes, pleuritis, and nephritis. Treatment for SLE aims to reduce disease activity and maintain a state of low inflammation. In this regard, numerous treatments are used, such as hydroxychloroquine, glucocorticoids, and non-glucocorticoid immunosuppressants such as methotrexate. Related to these drugs resulting in significant adverse effects and being ineffective in controlling SLE symptoms …

Akt Kinases As Therapeutic Targets, Dalal Hassan, Craig Menges, Joseph Testa, Alfonso Bellacosa

Student Papers, Posters & Projects

AKT, or protein kinase B, is a central node of the PI3K signaling pathway that is pivotal for a range of normal cellular physiologies that also underlie several pathological conditions, including inflammatory and autoimmune diseases, overgrowth syndromes, and neoplastic transformation. These pathologies, notably cancer, arise if either the activity of AKT or its positive or negative upstream or downstream regulators or effectors goes unchecked, superimposed on by its intersection with a slew of other pathways. Targeting the PI3K/AKT pathway is, therefore, a prudent countermeasure. AKT inhibitors have been tested in many clinical trials, primarily in combination with other drugs. While …

Beta-Blocker Use In Patients Undergoing Non-Cardiac Surgery: A Systematic Review And Meta-Analysis, Doménica Herrera Hernández, Bárbara Abreu, Tania S. Xiao, Andreina Rojas, Kevin López Romero, Valentina Contreras, Sol Villa Nogueyra, Zulma Sosa, Samantha M. Alvarez, Camila Sánchez Cruz, Ernesto Calderón Martinez

Department of Radiology Faculty Papers

BACKGROUND: The use of beta-blockers in the perioperative period has been widely investigated due to their potential to reduce the risk of major adverse cardiovascular and cerebrovascular events (MACCE) and mortality; yet their overall impact on various postoperative outcomes remains debated. This study constitutes a systematic review and meta-analysis of the impact of beta-blockers on mortality, MI, stroke, and other adverse effects such as hypotension and bradycardia in patients undergoing non-cardiac surgery.

METHODS: A comprehensive systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Searches were performed across PubMed, Cochrane, Web of Science, Scopus, EMBASE, and CINAHL databases; …

Systemic Effects Of Anti-Vegf Intravitreal Injection In Patients With Age-Related Macular Degeneration: A Multi-Institutional Real-World Study, Tzu-Yi Lin, Yi-Ting Hsieh, Sunir J. Garg, Lee-Jen Chen, Kuan-Jen Chen, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang, Eugene Yu-Chuan Kang

Wills Eye Hospital Papers

PURPOSE: In individuals aged >50 years, age-related macular degeneration (AMD) is the leading cause of irreversible blindness. Intravitreal injections of antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) show good efficacy and similar incidences of systemic adverse events (SAEs). However, comparative studies between agents are limited. Our study aimed to compare the real-world SAE risks of bevacizumab, ranibizumab, and aflibercept users.

METHODS: This retrospective cohort study identified new bevacizumab, ranibizumab, and aflibercept users in a multi-institutional database in Taiwan between 2014 and 2019. Inverse probability of treatment weights (IPTW) with propensity scores was conducted to achieve homogeneity among …

Deoxycholic Acid Injections As A Nonsurgical Treatment For Lipomas In Adiposis Dolorosa (Dercum Disease), Zvi Schwartz, Kayla Brockmeyer, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Adiposis dolorosa (Dercum disease) is a rare condition characterized by diffuse and recurring painful lipomas on the trunk and extremities. Patients are typically middle-aged females with an elevated BMI presenting with chronic pain. Physical examination reveals soft subcutaneous nodules and masses, tender to palpation. The associated pain significantly impacts quality of life and requires therapeutic intervention. The most common treatment option is surgical excision. Alternative options should be considered for patients with numerous lipomas where surgical management is not practical or is not desired. Deoxycholic acid injections are a viable alternative non-surgical technique. We present a case of a 55-year-old …

Identification Of The N-Terminal Residues Responsible For The Differential Microdomain Localization Of Cyp1a1 And Cyp1a2, Robert M. Fuchs, James R. Reed, J. Patrick Connick, Markéta Paloncýová, Martin Šrejber, Petra Čechová, Michal Otyepka, Marilyn K. Eyer, Wayne L. Backes

School of Graduate Studies Faculty Publications

The endoplasmic reticulum is organized into ordered regions enriched in cholesterol and sphingomyelin, and disordered microdomains characterized by more fluidity. Rabbit CYP1A1 and CYP1A2 localize into disordered and ordered microdomains, respectively. Previously, a CYP1A2 chimera containing the first 109 amino acids of CYP1A1 showed altered microdomain localization. The goal of this study was to identify specific residues responsible for CYP1A microdomain localization. Thus, CYP1A2 chimeras containing substitutions from homologous regions of CYP1A1 were expressed in HEK 293T/17 cells, and the localization was examined after solubilization with Brij 98. A CYP1A2 mutant with the three amino acids from CYP1A1 (VAG) at …

Antiplatelet Strategy For Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Systematic Review And Network Meta-Analysis, Waqas Ullah, Harigopal Sandhyavenu, Amro Taha, Smitha Narayana Gowda, Maryam Mukhtar, Aravind Reddy Polam, Salman Zahid, David L. Fischman, Michael P. Savage, Sunil V. Rao, Mohamad Alkhouli

Division of Cardiology Faculty Papers

BACKGROUND: Optimal duration and choice of antiplatelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention remain controversial.

METHODS AND RESULTS: Digital databases (PubMed, Cochrane, and Embase) were queried to select all randomized controlled trials on a post-percutaneous coronary intervention population with acute coronary syndrome. Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel for 12 months was compared with 4 major strategies: high-potency, high- to low-potency, low-dose, and short-duration DAPT. A network meta-analysis was performed to compare the safety and efficacy of different antiplatelet strategies. This study was the second updated manuscript under the International Prospective Register of Systematic …

Hyperbaric Oxygen Therapy In The Atls/Acls Resuscitative Management Of Acutely Ill Or Severely Injured Patients With Severe Anemia: A Review, Keith W. Van Meter

School of Medicine Faculty Publications

For short periods, even without the presence of red blood cells, hyperbaric oxygen can safely allow plasma to meet the oxygen delivery requirements of a human at rest. By this means, hyperbaric oxygen, in special instances, may be used as a bridge to lessen blood transfusion requirements. Hyperbaric oxygen, applied intermittently, can readily avert oxygen toxicity while meeting the body's oxygen requirements. In acute injury or illness, accumulated oxygen debt is shadowed by adenosine triphosphate debt. Hyperbaric oxygen efficiently provides superior diffusion distances of oxygen in tissue compared to those provided by breathing normobaric oxygen. Intermittent application of hyperbaric oxygen …

Cryo-Em Analysis Of Pseudomonas Phage Pa193 Structural Components, Stephano M. Iglesias, Chun-Feng Hou, Johnny Reid, Evan Schauer, Renae Geier, Angela Soriaga, Lucy Sim, Lucy Gao, Julian Whitelegge, Pierre Kyme, Deborah Birx, Sebastien Lemire, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

The World Health Organization has designated Pseudomonas aeruginosa as a critical pathogen for the development of new antimicrobials. Bacterial viruses, or bacteriophages, have been used in various clinical settings, commonly called phage therapy, to address this growing public health crisis. Here, we describe a high-resolution structural atlas of a therapeutic, contractile-tailed Pseudomonas phage, Pa193. We used bioinformatics, proteomics, and cryogenic electron microscopy single particle analysis to identify, annotate, and build atomic models for 21 distinct structural polypeptide chains forming the icosahedral capsid, neck, contractile tail, and baseplate. We identified a putative scaffolding protein stabilizing the interior of the capsid 5-fold …

The Effects Of Cannabinoids On Migration-Related Protein Expression In Ewing’S Sarcoma, Allison Lashall

Theses

Ewing’s sarcoma is an aggressive pediatric bone cancer that has low five-year survival rates, primarily due to metastatic disease and resistance of recurring tumors to traditional treatment options; therefore, novel treatment options are needed. The compound cannabidiol (CBD) has been shown to reduce cell viability, migration, and invasion in several tumor types, though the cellular mechanism of action is not well understood. Our lab has demonstrated the ability of CBD to reduce viability, migration, and invasion of Ewing’s sarcoma cells in vitro and is investigating differential protein and cytokine expression of known mediators of migration, such as intercellular adhesion molecule …

Managing Menopause: The Evolving Role Of Estrogens, Selective Serotonin Reuptake Inhibitors, And Phytoestrogens In Balancing Hormonal Fluctuations, Cassande Besong, Sandy Philippeaux, Ansa Bham, Naicha Gustinvil, Abigayle Castine, Giustino Varrassi, Patricia Sutker, Benjamin C. Miller, Caroline R. Burroughs, Sonja Gennuso, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Menopause is characterized by the cessation of menstruation for 12 consecutive months. In this narrative review, we describe the transitional stages of menopause, clinical presentation, pharmacological management of symptoms, and effects on fluctuating hormone levels. To standardize the stages of menopause, the Stages of Reproductive Aging Workshop + 10 (STRAW+10) system was designed with five distinct categories corresponding to symptom presentation and numerical years. Common clinical presentations consist of vasomotor hot flashes, mood changes, decreased libido, osteoporosis, and genitourinary changes, all of which are associated with changes in hormone levels. Because hormones play a major role in the mechanism of …

Providing End-Of-Life Counseling: A Narrative Inquiry, Carol Hecht, Sibyl West

Adultspan Journal

This qualitative study aimed to address the gap in the research related to end-of-life counseling by exploring the experiences of counselors working with clients at end of life. While counseling literature and education are lacking regarding end of life, many counselors will work alongside clients approaching death. The purpose of this study was twofold: (a) to better understand the nuanced experiences of counselors providing end-of-life counseling and (b) to explore the supports and preparations helpful for counselors to provide end-of-life counseling. A narrative approach, using the Listening Guide (Gilligan, 2015), was employed to analyze and present the stories of three …

Considerations Of Medicare Telehealth Services With Older Adults, Sonah Kho, Amanda Dediego

Adultspan Journal

The onset of the COVID-19 pandemic set in motion a rapid expansion of mental health services offered via telehealth. With this rapid expansion came the need to examine how policy and practice should be shaped in a future where telehealth is considered common in counseling practice. For counselors to understand how to support older adult clients in using telehealth services, they must understand telehealth policy. Following the eligibility of licensed counselors to participate in Medicare, counselors need to stay abreast of regulatory changes regarding restrictions and regulations on use of telehealth for mental and behavioral health services, including video and …

Removal Of Common Antimicrobial Agents By Sustained Low- Efficiency Dialysis, Joanna Q. Hudson Pharmd, Bcps, Fasn, Fccp, Madelyn N. Hilgers Bs, Pharmd Candidate, Elvira O. Gosmanova Md

Faculty Publications

Adequate dosing of antimicrobials is paramount for treating infections in critically ill patients undergoing kidney replacement therapy; however, little is known about antimicrobial removal by sustained low-efficiency dialysis (SLED). The objective was to quantify the removal of cefepime, daptomycin, meropenem, piperacillin–tazobactam, and vancomycin in patients undergoing SLED. Adult patients ≥18 years with acute kidney injury (AKI) or end-stage kidney disease receiving one of the select antimicrobials and requiring SLED were included. Blood and dialysate flow rates were maintained at 250 and 100 mL/min, respectively. Simultaneous arterial and venous blood samples for the analysis of antibiotic concentrations were collected hourly for …

Successful Treatment Of A Chronic Recurrent Expanding Hematoma Of The Thigh, Gianfranco Galantini, Bakhtawar Mushtaq, Jesse Ottaway, Charles Long

Abington Jefferson Health Papers

Chronic expanding hematoma (CEH) is a rare entity that poses diagnostic and therapeutic challenges due to persistent growth, risk of recurrence, and potential for blood loss anemia. The most common etiologies of CEH are trauma or surgery. It is thought to occur due to irritant effects of blood breakdown products, causing bleeding from capillaries in chronic granulation tissue. Although treatment of CEH is variable, complete surgical excision of the hematoma and its pseudocapsule is the gold standard. We present a case of a 15-year CEH that was initially treated with limited evacuation of the hematoma and cavity decortication, resulting in …

Complications And Influential Perioperative Factors Associated With Spaceoar Hydrogel Placement, Kerith Wang, Rishabh Simhal, Cassra Clark, Mark Mann, James Mark, Costas Lallas, Robert Den, Edouard Trabulsi

Department of Urology Faculty Papers

OBJECTIVE: To examine one academic institution's experiences with SpaceOAR placement, its associated complications, and periprocedural characteristics that affect outcomes for the purpose of quality improvement.

MATERIALS AND METHODS: We conducted a retrospective review of 233 patients who received SpaceOAR from four surgeons and one radiation oncologist between 2018 and 2021. Variables such as demographics, oncologic parameters, radiation plan, and radiographic assessment of hydrogel placement were recorded. The Charlson Comorbidity Index (CCI) was used to assess comorbidity risk. Mann-Whitney and Fisher's exact tests were performed to compare patients with and without complications.

RESULTS: Of the 233 patients who received SpaceOAR, 24 …

A Comparison Of The Safety And Efficacy Of Tapinarof And Roflumilast Topical Therapies In The Management Of Mild-To-Moderate Plaque Psoriasis, Hira Ghani, Alicia Podwojniak, Isabella J Tan, Aarushi K Parikh, Bianca Sanabria, Babar Rao

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Psoriasis is an immune-mediated inflammatory skin disease. First-line topical treatments include steroids, calcineurin inhibitors, vitamin D analogs, and anthralin. Recently, novel topical therapeutics like tapinarof and roflumilast have emerged with unique anti-inflammatory mechanisms and promising efficacy profiles.

MATERIALS AND METHODS: This review utilized PubMed, SCOPUS, and Web of Science databases to identify recent studies on tapinarof and roflumilast. Criteria focused on efficacy, safety profiles, and therapeutic roles in psoriasis treatment.

RESULTS: Four primary literature articles were identified for tapinarof and five for roflumilast. Both drugs demonstrated strong efficacy with minimal adverse events in treating mild-to-moderate plaque psoriasis. Tapinarof showed …

Exploring Perinatal Ketamine For Postpartum Depression Following Cesarean Section: A Systematic Review, Jaylyn Thompson, David F Lo, Alexis Foschini, Suvan Sundaresh

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The aim of this study was to explore the use of perinatal ketamine to see if it can be used for the reduction of postpartum depression (PPD) following cesarean section (C-section). PubMed, Cochrane, and Web of Science were the primary databases used for this review. Search terms used on January 5, 2024 incorporated "ketamine," "C-section," "postpartum depression," and related synonyms. The criteria for inclusion centered on studies published between January 1, 2008 and January 5, 2024. The final selection of articles was screened based on extraction criteria leaving eight randomized control trials in the final review. The selected data from …

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …