scholarly journals Injectable Nanoparticle-Based Hydrogels Enable the Safe and Effective Deployment of Immunostimulatory CD40 Agonist Antibodies

2021 ◽  
Author(s):  
Santiago Correa ◽  
Emily C Gale ◽  
Aaron T Mayer ◽  
Zunyu Xiao ◽  
Celine Liong ◽  
...  
Keyword(s):  
Drug Exposure ◽  
The Body ◽  
B16f10 Melanoma ◽  
Improve Treatment ◽  
Cytokine Induction ◽  
Technological Gap ◽  
Anti Cancer ◽  
Melanoma Model ◽  
Draining Lymph Node ◽  
Improve Treatment Efficacy

When properly deployed, the immune system can render deadly pathogens harmless, eradicate metastatic cancers, and provide long-lasting protection from diverse diseases. However, realizing these remarkable capabilities is inherently risky, as disruption to immune homeostasis can lead to dangerous complications and autoimmune disorders. While current research is continuously expanding the arsenal of potent immunotherapeutics, there is a technological gap when it comes to controlling when, where, and how long these drugs act on the body. Here, we explored the ability of a slow-releasing injectable hydrogel depot to reduce the problematic dose-limiting toxicities of immunostimulatory CD40 agonist antibodies (CD40a) while maintaining their potent anti-cancer efficacy. We previously described a polymer-nanoparticle (PNP) hydrogel system that is biocompatible, long lasting, and injectable, traits that we hypothesized would improve locoregional delivery of the CD40a immunotherapy. Using PET imaging, we found that hydrogels significantly improve CD40a pharmacokinetics by redistributing drug exposure to the tumor and the tumor draining lymph node (TdLN). Consistent with this altered biodistribution, hydrogel delivery significantly reduced weight loss, hepatotoxicity, and cytokine storm associated with treatment. Moreover, CD40a-loaded hydrogels were able to mediate improved local cytokine induction in the TdLN and improve treatment efficacy in both mono- and combination therapy settings in the B16F10 melanoma model. These results suggest that PNP hydrogels are a facile, drug-agnostic method to ameliorate immune-related adverse effects and explore locoregional delivery of immunostimulatory drugs.

Psychogenic Mass Syndrome in Anti-Cancer Drug Exposure

2010 ◽  
Author(s):  
N. Magnavita ◽  
I. lavicoli ◽  
V. Leso ◽  
A. Bergamaschi
Keyword(s):  
Drug Exposure ◽  
Cancer Drug ◽  
Anti Cancer

The antitoxic and protective effects of Curcuma longa and it`s active agent, Curcumin: оverview

2020 ◽  
pp. 66-72
Author(s):  
A. Khisamova ◽  
O. Gizinger
Keyword(s):  
Curcuma Longa ◽  
Physiological Activity ◽  
Active Agent ◽  
Modern Science ◽  
Physical Exertion ◽  
The Body ◽  
Modern World ◽  
Protective Effects ◽  
Daily Stress ◽  
Anti Cancer

In the modern world, where a person is exposed to daily stress, increased physical exertion, the toxic effect of various substances, including drugs. The task of modern science is to find antioxidants for the body. These can be additives obtained both synthetically and the active substances that we get daily from food. Such a striking example is turmeric, obtained from the plant Curcuma longa. Recently, it has been known that curcumin has an antioxidant, anti-inflammatory, anti-cancer effect and, thanks to these effects, plays an important role in the prevention and treatment of various diseases, in particular, from cancer to autoimmune, neurological, cardiovascular and diabetic diseases. In addition, much attention is paid to increasing the biological activity and physiological effects of curcumin on the body through the synthesis of curcumin analogues. This review discusses the chemical and physical characteristics, analogues, metabolites, the mechanisms of its physiological activity and the effect of curcumin on the body.

scholarly journals Mangiferin as New Potential Anti-Cancer Agent and Mangiferin-Integrated Polymer Systems—A Novel Research Direction

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 79
Author(s):  
Svetlana N. Morozkina ◽  
Thi Hong Nhung Vu ◽  
Yuliya E. Generalova ◽  
Petr P. Snetkov ◽  
Mayya V. Uspenskaya
Keyword(s):  
Molecular Mechanisms ◽  
Biological Activities ◽  
Research Direction ◽  
Biological Action ◽  
The Body ◽  
Biologically Active ◽  
Polymer Systems ◽  
Anti Cancer ◽  
Long Time ◽  
Cancer Agent

For a long time, the pharmaceutical industry focused on natural biologically active molecules due to their unique properties, availability and significantly less side-effects. Mangiferin is a naturally occurring C-glucosylxantone that has substantial potential for the treatment of various diseases thanks to its numerous biological activities. Many research studies have proven that mangiferin possesses antioxidant, anti-infection, anti-cancer, anti-diabetic, cardiovascular, neuroprotective properties and it also increases immunity. It is especially important that it has no toxicity. However, mangiferin is not being currently applied to clinical use because its oral bioavailability as well as its absorption in the body are too low. To improve the solubility, enhance the biological action and bioavailability, mangiferin integrated polymer systems have been developed. In this paper, we review molecular mechanisms of anti-cancer action as well as a number of designed polymer-mangiferin systems. Taking together, mangiferin is a very promising anti-cancer molecule with excellent properties and the absence of toxicity.

scholarly journals Dietary Curcumin: Correlation between Bioavailability and Health Potential

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2147 ◽  
Author(s):  
Michele Dei Cas ◽  
Riccardo Ghidoni
Keyword(s):  
Small Intestine ◽  
Cellular Uptake ◽  
Oral Delivery ◽  
Therapeutic Potential ◽  
Pharmacokinetic Profile ◽  
Yellow Pigment ◽  
The Body ◽  
Anti Cancer ◽  
Poor Absorption ◽  
Oral Delivery Systems

The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, hepatoprotective, anti-allergic, anti-dermatophyte, and neuroprotective. However, these properties are followed by a poor pharmacokinetic profile which compromises its therapeutic potential. The association of low absorption by the small intestine and the extensive reductive and conjugative metabolism in the liver dramatically weakens the oral bioavailability. Several strategies such as inhibition of curcumin metabolism with adjuvants as well as novel solid and liquid oral delivery systems have been tried to counteract curcumin poor absorption and rapid elimination from the body. Some of these drug deliveries can successfully enhance the solubility, extending the residence in plasma, improving the pharmacokinetic profile and the cellular uptake.

The relevance of therapeutic drug monitoring in plasma and erythrocytes in anti-cancer drug treatment

2004 ◽  
Vol 42 (11) ◽  
Author(s):  
Herlinde Dumez ◽  
Gunther Guetens ◽  
Gert De Boeck ◽  
Martin S. Highley ◽  
Robert A. A. Maes ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Drug Transport ◽  
Free Fraction ◽  
The Body ◽  
Cancer Drug ◽  
Therapeutic Drug ◽  
Anti Cancer ◽  
Plasma Compartment ◽  
Made In

AbstractTherapeutic drug monitoring generally focuses on the plasma compartment only. Differentiation between the total plasma concentration and the free fraction (plasma water) has been described for a number of limited drugs. Besides the plasma compartment, blood has also a cellular fraction which has by far the largest theoretical surface and volume for drug transport. It is with anti-cancer drugs that major progress has been made in the study of partition between the largest cellular blood compartment, i.e., erythrocytes, and the plasma compartment. The aim of the present review is to detail the progress made in predicting what a drug does in the body, i.e., pharmacodynamics including toxicity and plasma and/or red blood cell concentration monitoring. Furthermore, techniques generally used in anti-cancer drug monitoring are highlighted. Data for complex Bayesian statistical approaches and population kinetics studies are beyond the scope of this review, since this is generally limited to the plasma compartment only.

Locally Targeting the IL-17/IL-17RA Axis Reduced Tumor Growth in a Murine B16F10 Melanoma Model

2019 ◽  
Vol 30 (3) ◽  
pp. 273-285 ◽  
Author(s):  
Ya-Shan Chen ◽  
Tse-Hung Huang ◽  
Chao-Lin Liu ◽  
Hui-Shan Chen ◽  
Meng-Hua Lee ◽  
...  
Keyword(s):  
Tumor Growth ◽  
B16f10 Melanoma ◽  
Melanoma Model

scholarly journals Effects of N-acetyl-glucosamine-coated glycodendrimers as biological modulators in the B16F10 melanoma model in vivo

2014 ◽  
Vol 44 (4) ◽  
pp. 1410-1410 ◽  
Author(s):  
LUCA VANNUCCI ◽  
ANNA FISEROVÁ ◽  
KASHINATH SADALAPURE ◽  
THISBE K. LINDHORST ◽  
MARKETA KULDOVÁ ◽  
...  
Keyword(s):  
B16f10 Melanoma ◽  
Melanoma Model

Psoralidin exerts anti-tumor, anti-angiogenic, and immunostimulatory activities in 4T1 tumor‐bearing balb/c mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Davar Amani ◽  
Elham Shakiba ◽  
Ehsan Motaghi ◽  
Hiva Alipanah ◽  
Mahshad Jalalpourroodsari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Serum Level ◽  
Tumor Volume ◽  
Treated Group ◽  
The Body ◽  
Ki 67 ◽  
Tumor Bearing ◽  
Anti Cancer ◽  
Ifn Γ

Abstract Background Psoralidin as a compound of the Psoralea corylifolia seeds exhibited several anti-cancer potentials in various cancers. Materials and methods In this study, 4T1 tumor‐bearing Balb/c mice were treated by intraperitoneal administration of Psoralidin, and Paraffin, as a control group to investigate anti-tumor, anti-angiogenic, and immunostimulatory activities in breast cancer. Body weight and tumor volume measurement were performed. Hematoxylin and Eosin (H&E) staining as well as immunohistochemistry for Ki-67, CD31 and VEGF markers were conducted. In addition, ELISA assay was performed for evaluating the serum level of IFN-γ and IL-4. Moreover, real time assay was performed to evaluate the expression of angiogenesis and immunostimulatory related genes. Results There were no significant changes in the body weight of all animal groups. The anti-cancer effects of Psoralidin were significantly observed after 24 days of the last treatment, confirmed by smaller tumor volume and also H&E staining. The expression level of Ki‐67, CD31 and VEGF were significantly decreased in tumor tissues of the Psoralidin-treated group in comparison with Paraffin-treated group. Moreover, there was a significant reduction in the serum level of IL-4 in tumor-bearing mice after Psoralidin treatment while the serum level of IFN-γ was significantly augmented in all groups. Moreover, the reduction in expression of VEGF-a and IL-1β was observed. Interestingly Psoralidin treatment led to expression increase of FOXp3. Conclusions Psoralidin shows the anti-cancer potential in an animal model of breast cancer; however, further studies are recommended to elucidate its mechanisms of action.

Pharmacokinetics and Pharmacodynamics of Antimicrobials

2012 ◽  
pp. 3-13
Author(s):  
Lynn L. Estes
Keyword(s):  
Protein Binding ◽  
Antimicrobial Therapy ◽  
Drug Concentration ◽  
Drug Exposure ◽  
The Body ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Site Of Action ◽  
Pharmacologic Effect ◽  
Over Time

Pharmacokinetics is the disposition of drugs in the body (how the body acts on the drug); it incorporates terms such as absorption, bioavailability, distribution, protein binding, metabolism, and elimination. Pharmacodynamics is the interaction between the drug concentration at the site of action over time (drug exposure) and the pharmacologic effect, which, in the case of antimicrobials, is eradication of microorganisms. Pharmacokinetics and pharmacodynamics are interrelated. Both need to be taken into account to optimize antimicrobial therapy.

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