scholarly journals Mannosylated Polyrotaxanes for Increasing Cellular Uptake Efficiency in Macrophages through Receptor-Mediated Endocytosis

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 439 ◽  
Author(s):  
Kai Shibaguchi ◽  
Atsushi Tamura ◽  
Masahiko Terauchi ◽  
Mitsuaki Matsumura ◽  
Hiroyuki Miura ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Inflammatory Diseases ◽  
Specific Interaction ◽  
Mannose Receptor ◽  
Raw264.7 Cells ◽  
Intracellular Uptake ◽  
Macrophage Mannose Receptor ◽  
Selective Targeting ◽  
Poly Ethylene ◽  
Nih 3T3

Macrophages play an important role in the regulation of inflammation and immune response as well as the pathogenesis of chronic inflammatory diseases and cancer. Therefore, targeted delivery of therapeutic reagents to macrophages is an effective method for treatment and diagnosis. We previously examined the therapeutic applications of polyrotaxanes (PRXs) comprised of multiple cyclodextrins (CDs) threaded on a polymer chain and capped with bulky stopper molecules. In the present study, we designed an α-d-mannose-modified α-CD/poly(ethylene glycol)-based PRX (Man-PRX). The intracellular uptake of Man-PRX through the interaction with macrophage mannose receptor (MMR) in macrophage-like RAW264.7 cells was examined. Intracellular Man-PRX uptake was observed in MMR-positive RAW264.7 cells but was negligible in MMR-negative NIH/3T3 cells. In addition, the intracellular Man-PRX uptake in RAW264.7 cells was significantly inhibited in the presence of free α-d-mannose and an anti-MMR antibody, which suggests that MMR is involved in the intracellular uptake of Man-PRX. Moreover, the polarization of RAW264.7 cells affected the Man-PRX internalization efficiency. These results indicate that Man-PRX is an effective candidate for selective targeting of macrophages through a specific interaction with the MMR.

HIV Impairs Alveolar Macrophage Mannose Receptor Function Against Pneumocystis carinii

CHEST Journal ◽  
1993 ◽  
Vol 103 (2) ◽  
pp. 111S-112S ◽  
Author(s):  
Henry Koziel ◽  
B.A. Kruskal ◽  
R.A.B Ezekowitz ◽  
R.M Rose
Keyword(s):  
Alveolar Macrophage ◽  
Pneumocystis Carinii ◽  
Mannose Receptor ◽  
Receptor Function ◽  
Macrophage Mannose Receptor

scholarly journals A New Approach to Developing Long-Acting Injectable Formulations of Anti-HIV Drugs: Poly(Ethylene Phosphoric Acid) Block Copolymers Increase the Efficiency of Tenofovir against HIV-1 in MT-4 Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 340
Author(s):  
Ilya Nifant’ev ◽  
Andrei Siniavin ◽  
Eduard Karamov ◽  
Maxim Kosarev ◽  
Sergey Kovalchuk ◽  
...  
Keyword(s):  
Controlled Release ◽  
Block Copolymers ◽  
Phosphoric Acid ◽  
Hiv Infection ◽  
Targeted Delivery ◽  
Release Formulation ◽  
Poly Ethylene ◽  
Long Acting ◽  
Hiv Drugs ◽  
Anti Hiv

Despite the world’s combined efforts, human immunodeficiency virus (HIV), the causative agent of AIDS, remains one of the world’s most serious public health challenges. High genetic variability of HIV complicates the development of anti-HIV vaccine, and there is an actual clinical need for increasing the efficiency of anti-HIV drugs in terms of targeted delivery and controlled release. Tenofovir (TFV), a nucleotide-analog reverse transcriptase inhibitor, has gained wide acceptance as a drug for pre-exposure prophylaxis or treatment of HIV infection. In our study, we explored the potential of tenofovir disoproxil (TFD) adducts with block copolymers of poly(ethylene glycol) monomethyl ether and poly(ethylene phosphoric acid) (mPEG-b-PEPA) as candidates for developing a long-acting/controlled-release formulation of TFV. Two types of mPEG-b-PEPA with numbers of ethylene phosphoric acid (EPA) fragments of 13 and 49 were synthesized by catalytic ring-opening polymerization, and used for preparing four types of adducts with TFD. Antiviral activity of [mPEG-b-PEPA]TFD or tenofovir disoproxil fumarate (TDF) was evaluated using the model of experimental HIV infection in vitro (MT-4/HIV-1IIIB). Judging by the values of the selectivity index (SI), TFD exhibited an up to 14-fold higher anti-HIV activity in the form of mPEG-b-PEPA adducts, thus demonstrating significant promise for further development of long-acting/controlled-release injectable TFV formulations.

Dexamethasone Blocks the Interferon-γ-Mediated Downregulation of the Macrophage Mannose Receptor

1994 ◽  
Vol 312 (2) ◽  
pp. 367-374 ◽  
Author(s):  
V.L. Shepherd ◽  
H.B. Cowan ◽  
R. Abdolrasulnia ◽  
S. Vick
Keyword(s):  
Mannose Receptor ◽  
Interferon Γ ◽  
Macrophage Mannose Receptor

scholarly journals Inhaled antibiotics to improve efficacy and safety in the treatment of upper airway and lung inflammatory diseases

2021 ◽  
pp. 84-92
Author(s):  
Vladimir N. Drozdov ◽  
Konstantin I. Arefev ◽  
Svetlana Y. Serebrova ◽  
Irina A. Komissarenko ◽  
Evgenia V. Shikh ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Targeted Delivery ◽  
Whooping Cough ◽  
Inflammatory Diseases ◽  
Wide Spectrum ◽  
Chronic Obstructive ◽  
Combination Drug ◽  
Antibacterial Drugs ◽  
Systemic Antibiotic Therapy ◽  
Inhaled Antibiotics

Inhaled antibacterial drugs have been used since the 1940s with greater or lesser effectiveness, due to the possibility of targeted delivery of drugs directly to the infection site at concentrations higher than MICs. High local concentrations of antibacterial agents expand the possibilities of treating infections caused by multiresistant strains and reduces antibiotic resistance in the population. The inhaled delivery method is characterized by a high level of safety due to the absence of systemic toxic effects, which reduces the risk of pseudomembranous colitis and other complications of antibiotic therapy. Thiamphenicol glycinate acetylcysteinate is a combined drug that includes thiamphenicol and N-acetylcysteine, which causes its antibacterial and mucolytic activity. The results of clinical studies have demonstrated the effectiveness of TGA in the treatment of acute and chronic bronchitis, chronic obstructive pulmonary disease, community-acquired pneumonia, laryngotracheitis, rhinosinusitis and other infections of the upper and lower respiratory tract. In pediatrics, the drug is used to treat bronchitis and pneumonia, especially those that cannot be treated with other antibacterial drugs, bronchiolitis, whooping cough, and cystic fibrosis. The article presents data on the effectiveness and safety of containing TGA. A wide spectrum of antibacterial actions, the ability to form high local concentrations of antibacterial and mucolytic components in the focus of infection, a low risk of serious side effects in both adults and children are noted. The topical use of the combination drug has proven to be effective not only in bringing about a pronounced clinical improvement, but also in reducing the frequency of use of systemic antibiotic therapy. The efficacy of thiamphenicol glycinate acetylcysteinate is not inferior to macrolide antibiotics.

Sulphonated Poly(ethylene terephthalate)/Poly(3-hydroxy butyrate) Blends: Miscibility, Thermal Behavior, and Specific Interactions

e-Polymers ◽  
2007 ◽  
Vol 7 (1) ◽  
Author(s):  
Rafael Silva ◽  
Gizilene M. Carvalho ◽  
Edvani C. Muniz ◽  
Gentil J. Vidotti ◽  
Adley F. Rubira
Keyword(s):  
Carbonyl Group ◽  
Specific Interaction ◽  
Thermal Stabilities ◽  
Immiscible Blends ◽  
H Nmr ◽  
Miscible Blends ◽  
Poly Ethylene Terephthalate ◽  
Concentration Changes ◽  
Poly Ethylene ◽  
C Nmr

AbstractPETs/PHB blends with different compositions were produced by “casting” method. The blends were investigated by TGA, DSC, 1H and 13C NMR and FTIR. Phase separation occurred during blend preparation. PETs and PHB were present in both formed phases. The phases presented different thermal stabilities unrelated to phase component concentration changes. The miscibility study by DSC showed that PHB-phase rich blends are immiscible, whereas the PETs-rich phase blends are miscible. The 1H NMR spectra of the miscible blends exhibited a peak close to the PHB methylene signal, which is in accordance with the interaction between the PETs SO3 - groups and the PHB carbonyl groups. This interaction result in a shift of the PHB carbonyl group absorption band in the FTIR spectra and a variation in the chemical shift of the PHB carbonyl group resonance peak in solid state 13C NMR. No specific interaction was observed for the immiscible blends.

scholarly journals Absence of the Macrophage Mannose Receptor in Mice Does Not Increase Susceptibility to Pneumocystis carinii Infection In Vivo

2003 ◽  
Vol 71 (11) ◽  
pp. 6213-6221 ◽  
Author(s):  
Steve D. Swain ◽  
Sena J. Lee ◽  
Michel C. Nussenzweig ◽  
Allen G. Harmsen
Keyword(s):  
Pneumocystis Carinii ◽  
Hydrolytic Enzymes ◽  
Mannose Receptor ◽  
Opportunistic Pathogen ◽  
Cell Types ◽  
Surface Expression ◽  
Wild Type ◽  
Macrophage Mannose Receptor

ABSTRACT Host defense against the opportunistic pathogen Pneumocystis carinii requires functional interactions of many cell types. Alveolar macrophages are presumed to be a vital host cell in the clearance of P. carinii, and the mechanisms of this interaction have come under scrutiny. The macrophage mannose receptor is believed to play an important role as a receptor involved in the binding and phagocytosis of P. carinii. Although there is in vitro evidence for this interaction, the in vivo role of this receptor in P. carinii clearance in unclear. Using a mouse model in which the mannose receptor has been deleted, we found that the absence of this receptor is not sufficient to allow infection by P. carinii in otherwise immunocompetent mice. Furthermore, when mice were rendered susceptible to P. carinii by CD4+ depletion, mannose receptor knockout mice (MR-KO) had pathogen loads equal to those of wild-type mice. However, the MR-KO mice exhibited a greater influx of phagocytes into the alveoli during infection. This was accompanied by increased pulmonary pathology in the MR-KO mice, as well as greater accumulation of glycoproteins in the alveoli (glycoproteins, including harmful hydrolytic enzymes, are normally cleared by the mannose receptor). We also found that the surface expression of the mannose receptor is not downregulated during P. carinii infection in wild-type mice. Our findings suggest that while the macrophage mannose receptor may be important in the recognition of P. carinii, in vivo, this mechanism may be redundant, and the absence of this receptor may be compensated for.

Archidendron lucidum Exerts Anti-Inflammatory Effects by Targeting PDK1 in the NF-κB Pathway

2020 ◽  
Vol 48 (02) ◽  
pp. 429-444
Author(s):  
Minkyeong Jo ◽  
Young-Su Yi ◽  
Jae Youl Cho
Keyword(s):  
Signaling Pathway ◽  
Hplc Analysis ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Inflammatory Activity ◽  
Raw264.7 Cells ◽  
Luciferase Reporter ◽  
No Production ◽  
Pharmacological Activities ◽  
Anti Inflammatory

Pharmacological activities of some Leguminosae family members were reported. Pharmacological activities of Archidendron lucidum, a Leguminosae family member have never been explored. Therefore, this study investigated anti-inflammatory effects of an Archidendron lucidum methanol extract (Al-ME). In this study, anti-inflammatory effects of Al-ME were investigated in LPS-stimulated RAW264.7 cells and HCl/EtOH-induced gastritis mice by MTT assay, nitric oxide (NO) production assay, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), luciferase reporter assay, and Western blotting. High-performance liquid chromatography (HPLC) analysis identified ethnopharmacological compounds in Al-ME. Al-ME inhibited NO production without cytotoxicity in peritoneal macrophages and RAW264.7 cells stimulated with LPS or Pam3CSK4. Al-ME downregulated mRNA expression of inflammatory genes (inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2)) and pro-inflammatory cytokines (tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), and IL-6). Al-ME exerted anti-inflammatory activity in LPS-stimulated RAW264.7 cells by inhibiting nuclear factor-kappa B (NF-[Formula: see text]B) signaling pathway. HPLC analysis identified quercetin, luteolin, and kaempferol as major anti-inflammatory components in Al-ME. Al-ME ameliorated HCl/EtOH-induced gastritis symptoms in mice by suppressing iNOS and IL-6 mRNA expressions and I[Formula: see text]B[Formula: see text] phosphorylation. Therefore, these results suggest that Al-ME exhibited anti-inflammatory activity by targeting NF-[Formula: see text]B signaling pathway, implying that Al-ME could be potent anti-inflammatory medications to prevent and treat inflammatory diseases.

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