scholarly journals Oral Pharmacokinetics of a Chitosan-Based Nano- Drug Delivery System of Interferon Alpha

Polymers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1862 ◽  
Author(s):  
Julieta C. Imperiale ◽  
Inbar Schlachet ◽  
Marianela Lewicki ◽  
Alejandro Sosnik ◽  
Mirna M. Biglione
Keyword(s):  
Interferon Alpha ◽  
Viral Infections ◽  
Chitosan Nanoparticles ◽  
Area Under The Curve ◽  
Hydrodynamic Diameter ◽  
Cell Compatibility ◽  
Cell Monolayers ◽  
Pegylated Nanoparticles ◽  
Oral Pharmacokinetics ◽  
Poly Ethylene

Interferon alpha (IFNα) is a protein drug used to treat viral infections and cancer diseases. Due to its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability, which is associated with severe side effects. We hypothesized that the nanoencapsulation of IFNα within nanoparticles of the mucoadhesive polysaccharide chitosan would improve the oral bioavailability of this drug. In this work, we produced IFNα-loaded chitosan nanoparticles by the ionotropic gelation method. Their hydrodynamic diameter, polydispersity index and concentration were characterized by dynamic light scattering and nanoparticle tracking analysis. After confirming their good cell compatibility in Caco-2 and WISH cells, the permeability of unmodified and poly(ethylene glycol) (PEG)-modified (PEGylated) nanoparticles was measured in monoculture (Caco-2) and co-culture (Caco-2/HT29-MTX) cell monolayers. Results indicated that the nanoparticles cross the intestinal epithelium mainly by the paracellular route. Finally, the study of the oral pharmacokinetics of nanoencapsulated IFNα in BalbC mice revealed two maxima and area-under-the-curve of 56.9 pg*h/mL.

Central interferon-alpha inhibits natural killer cytotoxicity through sympathetic innervation

1993 ◽  
Vol 265 (2) ◽  
pp. R453-R459 ◽  
Author(s):  
S. Take ◽  
T. Mori ◽  
T. Katafuchi ◽  
T. Hori
Keyword(s):  
Natural Killer ◽  
Interferon Alpha ◽  
Viral Infections ◽  
Sympathetic Innervation ◽  
Nk Activity ◽  
Ifn Alpha ◽  
Nk Cytotoxicity ◽  
The Brain ◽  
Natural Killer Cytotoxicity ◽  
Crf System

The brain has been known to produce high levels of interferon-alpha (IFN-alpha) during viral infections. We investigated the central and peripheral mechanisms of the brain IFN-alpha-induced suppression of natural killer (NK) cytotoxicity in the rat. The activity of NK cells in the spleen and the peripheral blood decreased 30-120 min after intracerebroventricular (icv) injection of recombinant human IFN-alpha of > 1,000 U but not after its intraperitoneal injection. This effect was antagonized by pretreatment with icv naltrexone (NLTX). Splenic denervation was observed to completely abolish the IFN-alpha-induced suppression of NK activity, whereas bilateral adrenalectomy did not. Furthermore, this immunosuppression was blocked by an icv injection of an antagonist of corticotropin-releasing factor (CRF), alpha-helical CRF-(9-41). The icv injection of CRF resulted in reduced NK activity, which was not affected by NLTX. The results suggest that brain IFN-alpha activates the CRF system through central opioid receptors and thereby suppresses the NK cytotoxicity predominantly through splenic sympathetic innervation.

scholarly journals Using anti-poly(ethylene glycol) bioparticles for the quantitation of PEGylated nanoparticles

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yuan-Chin Hsieh ◽  
Ta-Chun Cheng ◽  
Hsin-Ell Wang ◽  
Jia-Je Li ◽  
Wen-Wei Lin ◽  
...  
Keyword(s):  
Ethylene Glycol ◽  
Poly Ethylene Glycol ◽  
Pegylated Nanoparticles ◽  
Poly Ethylene

scholarly journals Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats

Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 832 ◽  
Author(s):  
Kelly A. Deabold ◽  
Wayne S. Schwark ◽  
Lisa Wolf ◽  
Joseph J. Wakshlag
Keyword(s):  
Single Dose ◽  
Adverse Effects ◽  
Safety Data ◽  
Area Under The Curve ◽  
Pet Owners ◽  
Dose Oral ◽  
Oral Pharmacokinetics ◽  
Healthy Dogs ◽  
Clinically Significant

The use of CBD-rich hemp products is becoming popular among pet owners with no long-term safety data related to consumption in adult dogs and cats. The purpose of this study was to determine the single-dose oral pharmacokinetics of CBD, and to provide a preliminary assessment of safety and adverse effects during 12-week administration using a hemp-based product in healthy dogs and cats. Eight of each species were provided a 2 mg/kg total CBD concentration orally twice daily for 12 weeks with screening of single-dose pharmacokinetics in six of each species. Pharmacokinetics revealed a mean maximum concentration (Cmax) of 301 ng/mL and 43 ng/mL, area under the curve (AUC) of 1297 ng-h/mL and 164 ng-h/mL, and time to maximal concentration (Tmax) of 1.4 h and 2 h, for dogs and cats, respectively. Serum chemistry and CBC results showed no clinically significant alterations, however one cat showed a persistent rise in alanine aminotransferase (ALT) above the reference range for the duration of the trial. In healthy dogs and cats, an oral CBD-rich hemp supplement administered every 12 h was not detrimental based on CBC or biochemistry values. Cats do appear to absorb or eliminate CBD differently than dogs, showing lower serum concentrations and adverse effects of excessive licking and head-shaking during oil administration.

scholarly journals Bottlebrush-architectured poly(ethylene glycol) as an efficient vector for RNA interference in vivo

2019 ◽  
Vol 5 (2) ◽  
pp. eaav9322 ◽  
Author(s):  
Dali Wang ◽  
Jiaqi Lin ◽  
Fei Jia ◽  
Xuyu Tan ◽  
Yuyan Wang ◽  
...  
Keyword(s):  
Rna Interference ◽  
Ethylene Glycol ◽  
Target Genes ◽  
Area Under The Curve ◽  
Fold Increase ◽  
Small Interfering Rnas ◽  
Poly Ethylene Glycol ◽  
Linear Poly ◽  
Poly Ethylene

Nonhepatic delivery of small interfering RNAs (siRNAs) remains a challenge for development of RNA interference–based therapeutics. We report a noncationic vector wherein linear poly(ethylene glycol) (PEG), a polymer generally considered as inert and safe biologically but ineffective as a vector, is transformed into a bottlebrush architecture. This topology provides covalently embedded siRNA with augmented nuclease stability and cellular uptake. Consisting almost entirely of PEG and siRNA, the conjugates exhibit a ~25-fold increase in blood elimination half-life and a ~19-fold increase in the area under the curve compared with unmodified siRNA. The improved pharmacokinetics results in greater tumor uptake and diminished liver capture. Despite the structural simplicity these conjugates efficiently knock down target genes in vivo without apparent toxic and immunogenic reactions. Given the benign biological nature of PEG and its widespread precedence in biopharmaceuticals, we anticipate the brush polymer–based technology to have a significant impact on siRNA therapeutics.

scholarly journals Type I Interferon in Children with Viral or Bacterial Infections

2020 ◽  
Vol 66 (6) ◽  
pp. 802-808 ◽  
Author(s):  
Sophie Trouillet-Assant ◽  
Sébastien Viel ◽  
Antoine Ouziel ◽  
Lucille Boisselier ◽  
Philippe Rebaud ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Type I Interferon ◽  
Area Under The Curve ◽  
Pediatric Emergency ◽  
Type I ◽  
Discriminative Performance ◽  
Antibiotic Overuse ◽  
Reactive Protein

Abstract Background Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians’ decisions and limit antibiotic overuse. Methods Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. Results Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001). IFN-α concentrations and IFN score were significantly higher in viral compared to bacterial infection (P < 0.001). There was a strong correlation between serum IFN-α concentrations and IFN score (p-pearson = 0.83). Both serum IFN-α concentration and IFN score robustly discriminated (Area Under the Curve >0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). Conclusions IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. Clinical Trials Registration clinicaltrials.gov (NCT03163628).

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