Perspective: Dendrimer drugs for infection and inflammation

Shaunak, Sunil

doi:10.1016/j.bbrc.2015.07.033

Cited by 29 publications

(18 citation statements)

References 71 publications

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“…Our new finding of a large reduction of IL‐8, IL‐6, IL‐1 β and IFN‐ γ in the colon and rectum of NHPs (Figs and ) is consistent with DG blocking the cell surface TLR4–MYD88 early cytokine pathway of the TLR4‐MD‐2‐LPS receptor complex while sparing the endosomal TLR4‐TRIF/TRAM late cytokine and IFN‐ β /CD86 pathway . Maintaining TRIF signalling ensures an adequate gut pro‐inflammatory cytokine response for recruiting the neutrophils required to prevent the spread of pathogenic bacteria into tissues and blood.…”

Section: Discussionsupporting

confidence: 82%

“…This led us to propose that blocking the myeloid differentiation primary response gene 88 (MYD88) pathway of the TLR4‐MD‐2‐LPS‐mediated cytokine storm without interfering with the Toll/interleukin‐1 receptor (TIR) domain‐containing adapter‐inducing interferon‐β (TRIF)/TRIF‐related adaptor molecule (TRAM) pathway should prevent gut wall damage . We have previously modelled, synthesized and tested a 13 600 MW polyamidoamine dendrimer glucosamine and a 75% smaller 3300 MW polypropyletherimine dendrimer glucosamine (DG) in a rabbit closed intestinal loop model of Shigella flexneri infection.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Small dendrimer drugs are showing increasing promise as new polyvalent medicines in several animal models of infection and inflammation . Polypropyletherimine DG is a Good Manufacturing Process‐synthesized and analytically characterized generation 3 partially glycosylated dendrimer . It blocks the production of pro‐inflammatory cytokines by interfering with the electrostatic binding of: (i) the 4′ phosphate on the di‐glucosamine of LPS to Ser118 on MD‐2; (ii) LPS to Lys91 on MD‐2; and (iii) the subsequent binding of TLR4 to Tyr102 on MD‐2 .…”

Section: Introductionmentioning

confidence: 99%

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Controlling the cytokine storm in severe bacterial diarrhoea with an oral Toll‐like receptor 4 antagonist

et al. 2015

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SummaryShigella dysenteriae causes the most severe of all infectious diarrhoeas and colitis. We infected rhesus macaques orally and also treated them orally with a small and non-absorbable polypropyletherimine dendrimer glucosamine that is a Toll-like receptor-4 (TLR4) antagonist. Antibiotics were not given for this life-threatening infection. Six days later, the clinical score for diarrhoea, mucus and blood was 54% lower, colon interleukin-8 and interleukin-6 were both 77% lower, and colon neutrophil infiltration was 75% less. Strikingly, vasculitis did not occur and tissue fibrin thrombi were reduced by 67%. There was no clinical toxicity or adverse effect of dendrimer glucosamine on systemic immunity. This is the first report in non-human primates of the therapeutic efficacy of a small and orally bioavailable TLR antagonist in severe infection. Our results show that an oral TLR4 antagonist can enable controlled resolution of the infectionrelated-inflammatory response and can also prevent neutrophil-mediated gut wall necrosis in severe infectious diarrhoeas.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Controlling the cytokine storm in severe bacterial diarrhoea with an oral Toll‐like receptor 4 antagonist

et al. 2015

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“…Dendrimers are highly branched, nanodimention, symmetric molecules with well defined, homogenous and monodisperse structure that have attracted great attention in biomedical applications. Application of dendrimers for the development of anti‐cancer, anti‐inflammatory, and antiviral drugs could be of great interest in the field of oncology and infectious diseases. Dendrimers are also used as carrier molecules for drug delivery, gene transfer and in homogeneous as well as heterogeneous catalysis .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Photophysical Property and Antibacterial Activity of Rhodamine B Decorated, Mesitylene Cored and Methylene p‐Phenoxy Bridged Dendrimers

Savithri

Rajakumar

2019

ChemistrySelect

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Rhodamine B decorated, mesitylene cored and methylene pphenoxy bridged dendrimers 1-3 were synthesized upto second generation in good yield by divergent methodology. The intensity of the UV-Visible absorption and emission band increases on increasing the number of the dendritic wedges.The antibacterial activity of the dendrimer 3 was found to be better than the lower generation dendrimers 1 and 2 against both the gram positive and gram negative bacteria such as B. subtilis, S. aureus, E. coli and P. aeruginosa.[a] J.

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'Plate‐like‐coral' polymer particles with dendritic structure and porous channels: Effective delivery of anti‐cancer drugs

Amgoth

Dharmapuri

Patra

et al. 2020

J of Applied Polymer Sci

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'Plate‐like‐coral' shaped polymer capsule (PC‐PLCDB) with dendritic network structure and porous channels has been synthesized and used for therapeutic purposes. First di‐block copolymer [(PEG)‐b‐(L‐AspA)n] has been synthesized from PEG (polyethylene glycol) and aspartic acid (AspA). Then the biocompatible PC‐PLCDB has been achieved by homogeneous mixing of [(PEG)‐b‐(L‐AspA)n] and poly‐N‐isopropyl acrylamide (PNIPAM) followed by reprecipitation. Only H‐bonding is responsible for the foundation of self‐assembly of the polymer chains and to form PC‐PLCDB. A huge extent of loading anticancer drug, for example, doxorubicin (DOX) in PC‐PLCDB is possible. in vitro study has been performed to check the therapeutic efficacy of PC‐PLCAD‐DOX formulation on chronic myeloid leukemia cells (K562). The IC50 has been calculated to be 0.405 (±0.014) ng μg−1 of the formulation. PC‐PLCAD‐DOX inhibits 80% of the cancer cell only by 1.0 μg mL−1 of the formulation. This study reveals that the PC‐PLCAD could be a promising candidate for therapeutic applications.

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Perspective: Dendrimer drugs for infection and inflammation

Cited by 29 publications

References 71 publications

Controlling the cytokine storm in severe bacterial diarrhoea with an oral Toll‐like receptor 4 antagonist

Controlling the cytokine storm in severe bacterial diarrhoea with an oral Toll‐like receptor 4 antagonist

Synthesis, Photophysical Property and Antibacterial Activity of Rhodamine B Decorated, Mesitylene Cored and Methylene p‐Phenoxy Bridged Dendrimers

'Plate‐like‐coral' polymer particles with dendritic structure and porous channels: Effective delivery of anti‐cancer drugs

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