Targeting bacterial virulence as a novel treatment against AMR infections

drug development, ,

Have you known that Arivin Therapeutics uses cyclodextrin for targeting bacterial virulence as a novel treatment against AMR infections? Among their MoA claims, the following are listed:
– Targeting virulence factors is effective, also against extensively resistant isolates
– Targeting virulence avoids rapid resistance
– Direct reduction in inflammatory responses
– Potentiates the function of antibiotics
Also, there is a spectacular video about how CDs develop their effect as antibacterials.

https://arivintx.com/our-science

Hydroxypropyl-β-cyclodextrin inhibits the development of triple-negative breast cancer by enhancing antitumor immunity

drug development, ,

After sharing news on treating lymphedema, we came across another potential therapeutic use of cyclodextrin. In this preprint from Hefei University of Technology and Emory University authors demonstrate that 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) inhibited the growth and metastasis of triple-negative breast cancer (TNBC) both in vitro and in vivo, although the underlying mechanisms are unclear.
Cholesterol supplementation can attenuate HP-b-CD-inhibited TNBC growth and metastasis both in vitro and in vivo. In vivo, HP-β-CD promoted the infiltration of T cells into the tumor microenvironment (TME) and improved the exhaustion of CD8+ T cells via reducing endoplasmic reticulum (ER) stress and immune checkpoint molecules. Additionally, HP-β-CD inhibited the recruitment of tumor-associated macrophages to the TME by reducing the CCL2-p38MAPK-NF-kB axis. HP-β-CD also inhibited the epithelial-mesenchymal transition (EMT) of TNBC cells mediated by transforming the growth factor-b (TGF-b) signaling pathway.
In summary, the data in the current study suggest that HP-β-CD effectively inhibited the proliferation and metastasis of TNBC and melanoma, highlighting HP-β-CD may be a potential general antitumor clinical drug.

See the full article here

The authors found that HP-b-CD inhibits the proliferation and metastasis of TNBC by reducing cholesterol levels. HP-b-CD promotes T cell recruitment to the TME and improves CD8+ T cell exhaustion. Additionally, HP-b-CD inhibits TAMs accumulation.

Pillar[6]MaxQ: A potent supramolecular host for in vivo sequestration of methamphetamine and fentanyl

drug development,

Lyle Isaacs and his team from University of Maryland has something fascinating to show. Not only have they published a potent supramolecular host for in vivo sequestration of methamphetamine and fentanyl (similar to the Sugammadex concept) but they also shared this cool video on the mechanism of action: UMD Researcher Creates Chemical Compound That Can Reverse Effects of Potentially Deadly Drugs – YouTube

This is how you should present science! Amazing!
Adam Brockett, Canjia Zhai, Shivangi Rastogi, Volker Briken

See the full article here

Comparison of the Efficacy and Safety of Adamgammadex with Sugammadex for Reversal of Rocuronium-Induced Neuromuscular Block: Results of a Phase II Clinical Trial

drug development, drug discovery, , ,

The success of Sugammadex inspired several further cyclodextrin research, including the development of other antidotes and discovering “follow-up” compounds for the same indication. The most advanced candidate in this field is Adamgammadex (developed by Adamerck) with its efficacy recently compared to SGM in a Phase II trial lead by Sichuan University. Although it was used in 2-3 times higher concentrations, the previously reported adverse effects were not observed in this study, including anaphylaxis, haemorrhage, recurarization, abnormal basic vital signs, or lengthened QRS intervals and QT intervals. Adamgammadex was found to be effective for reversing rocuronium-induced neuromuscular block as sugammadex.

See the full article here

Beren Awarded Expedited Roadmap for Treatment of Homozygous Familial Hypercholesterolemia

drug development, , , , ,

Fascinating news from Beren Therapeutics:
Beren Awarded Expedited Roadmap for Treatment of Homozygous Familial Hypercholesterolemia
Beren’s novel lead asset, BRN-002, was awarded an Innovation Passport under the United Kingdom’s Innovative Licensing and Access Pathway (ILAP), for the reversal of atherosclerosis in patients with Homozygous Familial Hypercholesterolemia. The ILAP aims to accelerate the time to market for innovative medicines that address the needs of patients with life-threatening or seriously debilitating diseases.
“We are excited to begin work under ILAP and look forward to collaborating with other regulators, payors, and governments to expedite the development and identify and remove access barriers.” – commented Jason Camm, CEO. Jules Payne from HEART UK – The Cholesterol Charity added that “Significant unmet needs remain, and with this advancement, we are hopeful for a new treatment option that can truly alter the course of the disease for the children and patients living with HoFH.”
Beren Therapeutics, P.B.C. is currently in stealth.

See the full article here

Weekly round-up of other carbohydrate-related articles (2022/47)

carbohydrates, drug delivery, drug development, drug discovery

I.
Great review from Universidade de Coimbra (Ana Cláudia Paiva-Santos, Laura Ferreira, Filipa Mascarenhas Melo, Sofia Rabaça, Francisco Veiga), Mewar University (Dr. Ankita Mathur), Sharda University, University at Buffalo (Dr. Prabhanjan Giram), Shivaji University, University of Zabol (Abbas Rahdar), Shanghai Jiao Tong University (Faisal Raza 费赛), Faculdade de Ciências Farmacêuticas – Unicamp (ENG: Pharmacy School – University of Campinas) (Priscila Mazzola) on dermatology and cosmetic applications

Read the full article here

II.
Beta-Cyclodextrins as affordable antivirals to treat coronavirus infection

Read the full article here

III.
Honestly, I am not sure how mankind will handle medication related to space travel. That will be a huge challenge that needs to be studied asap. Recently, the interaction behavior of remdesivir with CDs was studied at ISS (pp 53)

See the NASA e-book here

IV.
How cool is it that you can use CDs to stabilize antigens? Super cool 🙂
Polypseudorotaxane hydrogels based on cyclodextrin and polyethylene glycol significantly improved the stability of antibody preparations and showed no serious adverse effects after subcutaneous injection, suggesting the possibility as safe vaccine formulations to stabilize an antigen protein.
Daiichi University of Pharmacy
Kumamoto University, JAPAN
Hiroshi Itou Hidetoshi Arima Keiichi Motoyama

Read the full article here

V.
Enrichment of bread with α-CD resulted in positive effects on postprandial glycaemia and induced satiety. The incorporation of encapsulated hydroxytyrosol offered similar overall acceptability due to the bitter taste-masking effect provided by α-CD and a slightly additional positive effect in postprandial glycaemia and satiety. The development of foods with favorable metabolic effects is of great importance for the prevention of chronic diseases. The study was prospectively registered in clinicaltrials.gov (NCT04725955, date: 27th January 2021).
Harokopio University of Athens – Panagiota Binou, Athena Stergiou, Nikolaos Tentolouris, Vaios K.

See the full article here

VI.
Is the humid autumn whether messing up your hair? Keep calm and use CD-formulations (L’Oréal invention – Cho-Cho Khine and Ronak Rughani) for providing lasting curl definition and/or frizz and/or volume control to hair, even in high humidity.

See the full patent here

Effects of Hydroxypropyl-Beta-Cyclodextrin on Cultured Brain Endothelial Cells

drug development, , ,

Heartwarming to see such important findings published by Hungarian researchers on the effects of Hydroxypropyl-beta-cyclodextrin on Cultured Brain Endothelial Cells. Cytotoxicity, permeability, and cellular internalization of HPBCD on primary rat and immortalized human (hCMEC/D3) brain capillary endothelial cells were investigated, which can help to develop new strategies for improved HPBCD effects after systemic administration.

See the full article

carbohyde, cyclodextrin, brain