Resveratrol-Zinc Nanoparticles for COVID-19 Management: Potential Other Inflammatory, Immunologic and Oncologic Benefits.

Mapping Intimacies ◽

10.31219/osf.io/2ngqj ◽

2021 ◽

Author(s):

Mina Kelleni

Keyword(s):

Drug Delivery ◽

Clinical Trials ◽

Adjuvant Therapy ◽

Red Wine ◽

Severe Disease ◽

Peanut Butter ◽

Scientific Basis ◽

Zinc Nanoparticles ◽

Red Grapes ◽

Oncologic Diseases

A peer reviewed published version is found here: https://www.sciencedirect.com/science/article/pii/S075333222100411X?via%3Dihub In this manuscript we provide the scientific basis to adopt a novel combination of two widely available nutraceuticals; resveratrol and zinc in management of COVID-19 recommending their administration using a nano-carrier based drug-delivery system. Resveratrol, a well-known antioxidant and anti-inflammatory triphenolic stilbene, is abundant in red grapes, red wine, dark chocolate, and peanut butter. Alternatively, pterostilbene-zinc combination might be also considered for clinical trials. We recommend conducting prompt clinical trials to assess the potential of the suggested combinations as a monotherapy for mild COVID-19 with a potential to prevent its progression to moderate-severe disease for which we also recommend its trial as an adjuvant therapy. Furthermore, he suggested combinations might also possess a pharmacotherapeutic potential that exceeds COVID-19 to various inflammatory, immunologic, and oncologic diseases.

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Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines

Vaccines ◽

10.3390/vaccines9040359 ◽

2021 ◽

Vol 9 (4) ◽

pp. 359

Author(s):

Thai Thanh Hoang Thi ◽

Estelle J. A. Suys ◽

Jung Seok Lee ◽

Dai Hai Nguyen ◽

Ki Dong Park ◽

...

Keyword(s):

Drug Delivery ◽

Clinical Trials ◽

Physicochemical Properties ◽

Solid Lipid Nanoparticles ◽

Drug Delivery Systems ◽

Lipid Nanoparticles ◽

Therapeutic Vaccines ◽

Cancer Nanomedicine ◽

Fundamental Research ◽

Further Development

COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil® and Onpattro®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.

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IMG-09. RESPONSE ASSESSMENT IN DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG): RECOMMENDATIONS FROM THE RESPONSE ASSESSMENT IN PEDIATRIC NEURO-ONCOLOGY COMMITTEE

Neuro-Oncology ◽

10.1093/neuonc/noaa222.345 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii356-iii357

Author(s):

Tabitha Cooney ◽

Kenneth J Cohen ◽

Carolina V Guimaraes ◽

Girish Dhall ◽

James Leach ◽

...

Keyword(s):

Drug Delivery ◽

Clinical Trials ◽

Response Duration ◽

Response Assessment ◽

Diffuse Intrinsic Pontine Glioma ◽

Pontine Glioma ◽

Response Data ◽

International Panel ◽

Children And Young Adults ◽

Magnetic Resonance Imaging Mri

Abstract Optimizing the conduct of clinical trials for diffuse intrinsic pontine glioma (DIPG) involves use of consistent, objective disease assessments and standardized response criteria. The Response Assessment in Pediatric Neuro-Oncology (RAPNO) committee, an international panel of pediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address unique challenges in assessing response in children with CNS tumors. A subcommittee of RAPNO was formed to specifically address response assessment in children and young adults with DIPG and to develop a consensus on recommendations for response assessment. Distinct issues related to the response assessment of DIPG include its definition and recent molecular classifications, dearth of imaging response data, the phenomena of pseudoprogression, and measuring response in the era of focal drug delivery. The committee has recommended response be assessed using magnetic resonance imaging (MRI) of brain and spine, neurologic examination, and use of supportive medication, i.e. steroids and anti-angiogenic agents. Clinical imaging standards and imaging quality control are defined. Unique recommendations for DIPG response include an eight-week response duration, a twenty-five percent decrease for partial response, and the distinction of pontine and extra-pontine response for trials that use focal drug delivery. The recommendations presented here represent an initial effort to uniformly collect and evaluate response assessment criteria; these recommendations can now be incorporated into clinical trials to assess feasibility and corroboration with patient outcomes.

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Adjuvant Therapy for High Risk Localized Kidney Cancer: Emerging Evidence and Future Clinical Trials

The Journal of Urology ◽

10.1016/j.juro.2017.04.092 ◽

2018 ◽

Vol 199 (1) ◽

pp. 43-52 ◽

Cited By ~ 18

Author(s):

Andrew T. Lenis ◽

Nicholas M. Donin ◽

David C. Johnson ◽

Izak Faiena ◽

Amirali Salmasi ◽

...

Keyword(s):

Clinical Trials ◽

High Risk ◽

Adjuvant Therapy ◽

Kidney Cancer

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Convection-enhanced delivery to the central nervous system

Journal of Neurosurgery ◽

10.3171/2014.10.jns14229 ◽

2015 ◽

Vol 122 (3) ◽

pp. 697-706 ◽

Cited By ~ 85

Author(s):

Russell R. Lonser ◽

Malisa Sarntinoranont ◽

Paul F. Morrison ◽

Edward H. Oldfield

Keyword(s):

Drug Delivery ◽

Central Nervous System ◽

Clinical Trials ◽

Nervous System ◽

Convective Flow ◽

Clinical Applications ◽

Systemic Delivery ◽

Convection Enhanced Delivery ◽

The Central Nervous System ◽

Real Time Tracking

Convection-enhanced delivery (CED) is a bulk flow–driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

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Increasing the Power of Polyphenols through Nanoencapsulation for Adjuvant Therapy against Cardiovascular Diseases

Molecules ◽

10.3390/molecules26154621 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4621

Author(s):

Lucileno Rodrigues Trindade ◽

Davi Vieira Teixeira da da Silva ◽

Diego dos Santos Baião ◽

Vania Margaret Flosi Paschoalin

Keyword(s):

Clinical Trials ◽

Cardiovascular Diseases ◽

Adjuvant Therapy ◽

Vascular Diseases ◽

Ppar Γ ◽

Epidemiological Surveys ◽

Genes Encoding ◽

And Oxidative Stress ◽

Gradual Release ◽

Inflammatory Action

Polyphenols play a therapeutic role in vascular diseases, acting in inherent illness-associate conditions such as inflammation, diabetes, dyslipidemia, hypertension, and oxidative stress, as demonstrated by clinical trials and epidemiological surveys. The main polyphenol cardioprotective mechanisms rely on increased nitric oxide, decreased asymmetric dimethylarginine levels, upregulation of genes encoding antioxidant enzymes via the Nrf2-ARE pathway and anti-inflammatory action through the redox-sensitive transcription factor NF-κB and PPAR-γ receptor. However, poor polyphenol bioavailability and extensive metabolization restrict their applicability. Polyphenols carried by nanoparticles circumvent these limitations providing controlled release and better solubility, chemical protection, and target achievement. Nano-encapsulate polyphenols loaded in food grade polymers and lipids appear to be safe, gaining resistance in the enteric route for intestinal absorption, in which the mucoadhesiveness ensures their increased uptake, achieving high systemic levels in non-metabolized forms. Nano-capsules confer a gradual release to these compounds, as well as longer half-lives and cell and whole organism permanence, reinforcing their effectiveness, as demonstrated in pre-clinical trials, enabling their application as an adjuvant therapy against cardiovascular diseases. Polyphenol entrapment in nanoparticles should be encouraged in nutraceutical manufacturing for the fortification of foods and beverages. This study discusses pre-clinical trials evaluating how nano-encapsulate polyphenols following oral administration can aid in cardiovascular performance.

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Is there a role for adjuvant therapy after surgery in “high risk for recurrence” kidney cancer? An update on current concepts

Current Oncology ◽

10.3747/co.25.3865 ◽

2018 ◽

Vol 25 (5) ◽

Cited By ~ 3

Author(s):

T. Sharma ◽

C. Tajzler ◽

A. Kapoor

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

High Risk ◽

Adjuvant Therapy ◽

Patient Population ◽

Treatment Options ◽

Significant Proportion ◽

High Risk Patient ◽

Disease Free Survival ◽

Cochrane Reviews

BackgroundAlthough surgical resection remains the standard of care for localized kidney cancers, a significant proportion of patients experience systemic recurrence after surgery and hence might benefit from effective adjuvant therapy. So far, several treatment options have been evaluated in adjuvant clinical trials, but only a few have provided promising results. Nevertheless, with the recent development of targeted therapy and immunomodulatory therapy, a series of clinical trials are in progress to evaluate the potential of those novel agents in the adjuvant setting. In this paper, we provide a narrative review of the progress in this field, and we summarize the results from recent adjuvant trials that have been completed.MethodsA literature search was conducted. The primary search strategy at the medline, Cochrane reviews, and http://ClinicalTrials.gov/ databases included the keywords “adjuvant therapy,” “renal cell carcinoma,” and “targeted therapy or/and immunotherapy.”ConclusionsData from the s-trac study indicated that, in the “highest risk for recurrence” patient population, disease-free survival was increased with the use of adjuvant sunitinib compared with placebo. The assure trial showed no benefit for adjuvant sunitinib or sorafenib in the “intermediate- to high-risk” patient population. The ariser (adjuvant girentuximab) and protect (adjuvant pazopanib) trials indicated no survival benefit, but subgroup analyses in both trials recommended further investigation. The inconsistency in some of the current results can be attributed to a variety of factors pertaining to the lack of standardization across the trials. Nevertheless, patients in the “high risk of recurrence” category after surgery for their disease would benefit from a discussion about the potential benefits of adjuvant treatment and enrolment in ongoing adjuvant trials.

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Adjuvant Therapy for Breast Cancer: Recommendations for Management Based on Consensus Review and Recent Clinical Trials

The Oncologist ◽

10.1634/theoncologist.7-3-246 ◽

2002 ◽

Vol 7 (3) ◽

pp. 246-250 ◽

Cited By ~ 22

Author(s):

Betty A. Mincey ◽

Frances M. Palmieri ◽

Edith A. Perez

Keyword(s):

Breast Cancer ◽

Clinical Trials ◽

Adjuvant Therapy

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Status Quo and Trends of Intra-Arterial Therapy for Brain Tumors: A Bibliometric and Clinical Trials Analysis

Pharmaceutics ◽

10.3390/pharmaceutics13111885 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1885

Author(s):

Julian S. Rechberger ◽

Frederic Thiele ◽

David J. Daniels

Keyword(s):

Drug Delivery ◽

Clinical Trials ◽

Brain Tumors ◽

Phase 1 ◽

Citation Count ◽

Tumor Therapy ◽

The United States ◽

Blood Brain Barrier Disruption ◽

Current State ◽

Brain Barrier Disruption

Intra-arterial drug delivery circumvents the first-pass effect and is believed to increase both efficacy and tolerability of primary and metastatic brain tumor therapy. The aim of this update is to report on pertinent articles and clinical trials to better understand the research landscape to date and future directions. Elsevier’s Scopus and ClinicalTrials.gov databases were reviewed in August 2021 for all possible articles and clinical trials of intra-arterial drug injection as a treatment strategy for brain tumors. Entries were screened against predefined selection criteria and various parameters were summarized. Twenty clinical trials and 271 articles satisfied all inclusion criteria. In terms of articles, 201 (74%) were primarily clinical and 70 (26%) were basic science, published in a total of 120 different journals. Median values were: publication year, 1986 (range, 1962–2021); citation count, 15 (range, 0–607); number of authors, 5 (range, 1–18). Pertaining to clinical trials, 9 (45%) were phase 1 trials, with median expected start and completion years in 2011 (range, 1998–2019) and 2022 (range, 2008–2025), respectively. Only one (5%) trial has reported results to date. Glioma was the most common tumor indication reported in both articles (68%) and trials (75%). There were 215 (79%) articles investigating chemotherapy, while 13 (65%) trials evaluated targeted therapy. Transient blood–brain barrier disruption was the commonest strategy for articles (27%) and trials (60%) to optimize intra-arterial therapy. Articles and trials predominately originated in the United States (50% and 90%, respectively). In this bibliometric and clinical trials analysis, we discuss the current state and trends of intra-arterial therapy for brain tumors. Most articles were clinical, and traditional anti-cancer agents and drug delivery strategies were commonly studied. This was reflected in clinical trials, of which only a single study had reported outcomes. We anticipate future efforts to involve novel therapeutic and procedural strategies based on recent advances in the field.

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Complementary role of mathematical modeling in preclinical glioblastoma: differentiating poor drug delivery from drug insensitivity

10.1101/2021.12.07.471540 ◽

2021 ◽

Author(s):

Javier C. Urcuyo ◽

Susan Christine Massey ◽

Andrea Hawkins-Daarud ◽

Bianca-Maria Marin ◽

Danielle M. Burgenske ◽

...

Keyword(s):

Mathematical Modeling ◽

Drug Delivery ◽

Clinical Trials ◽

Treatment Response ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Significant Heterogeneity ◽

Current Standard ◽

Modeling Approach ◽

Blood Brain

AbstractGlioblastoma is the most malignant primary brain tumor with significant heterogeneity and a limited number of effective therapeutic options. Many investigational targeted therapies have failed in clinical trials, but it remains unclear if this results from insensitivity to therapy or poor drug delivery across the blood-brain barrier. Using well-established EGFR-amplified patient-derived xenograft (PDX) cell lines, we investigated this question using an EGFR-directed therapy. With only bioluminescence imaging, we used a mathematical model to quantify the heterogeneous treatment response across the three PDX lines (GBM6, GBM12, GBM39). Our model estimated the primary cause of intracranial treatment response for each of the lines, and these findings were validated with parallel experimental efforts. This mathematical modeling approach can be used as a useful complementary tool that can be widely applied to many more PDX lines. This has the potential to further inform experimental efforts and reduce the cost and time necessary to make experimental conclusions.Author summaryGlioblastoma is a deadly brain cancer that is difficult to treat. New therapies often fail to surpass the current standard of care during clinical trials. This can be attributed to both the vast heterogeneity of the disease and the blood-brain barrier, which may or may not be disrupted in various regions of tumors. Thus, while some cancer cells may develop insensitivity in the presence of a drug due to heterogeneity, other tumor areas are simply not exposed to the drug. Being able to understand to what extent each of these is driving clinical trial results in individuals may be key to advancing novel therapies. To address this challenge, we used mathematical modeling to study the differences between three patient-derived tumors in mice. With our unique approach, we identified the reason for treatment failure in each patient tumor. These results were validated through rigorous and time-consuming experiments, but our mathematical modeling approach allows for a cheaper, quicker, and widely applicable way to come to similar conclusions.

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