Avoiding Interferences in Advance: Cyclodextrin Polymers to Enhance Selectivity in Extraction of Organic Micropollutants for Carbon Isotope Analysis

Today's cyclodextrin,

today’s cyclodextrin:
CDs in carbon isotope analysis
Compound-specific isotope analysis (CSIA) of organic water contaminants can provide important information about their sources and fate in the environment. Analyte enrichment from water remains nonetheless a critical yet inevitable step before measurement. Commercially available solid-phase extraction (SPE) sorbents are inherently nonselective leading to co-extraction of concurrent dissolved organic matter and in turn to analytical interferences, especially for low-occurring contaminants. Using cyclodextrin polymers (α-, β-, γ-CDP) as SPE sorbents (i) extraction selectivity was increased, (ii) their applicability to carbon isotope analysis for a selection of pesticides was assessed, and (iii) they were compared with commonly used commercial sorbents. Extraction with β-CDP significantly reduced backgrounds in gas chromatography-isotope ratio mass spectrometry (GC-IRMS) and enhanced sensitivity by a factor of 7.5, which was further confirmed by lower carbon-normalized CDOM/Canalyte ratios in corresponding extracts as derived from dissolved organic carbon (DOC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The present study highlights the benefit of selecting innovative extraction sorbents to avoid interferences in advance. This strategy in combination with existing cleanup approaches offers new prospects for CSIA at field concentrations of tens to hundreds of nanograms per liter.

Martin Elsner and Rani Bakkour et al

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Cyclodextrins in Biopharma on June 21, 2023

news,

This free webinar series explores the present and future applications of cyclodextrins in biopharma through a series of educative sessions. It focuses on cyclodextrin uses in protein formulations (monoclonal antibodies), gene therapy, vaccines, and other biotech applications. The webinar includes an overview of the current market, three concise lectures by experts from Roquette and CarboHyde, and concludes with a moderated panel discussion featuring the speakers and key opinion leaders.

The audience can ask questions and participate in an open discussion about the challenges and possibilities of these innovative applications.

You can register here: Cyclodextrin in Biopharma (and more details about the program and experts)

Program

  • BioPharma Market Insights (15 min)
    Elham Blouet, Regional Head Bio Pharma Technology, Roquette
  • Revolutionizing Gene Therapy: The Dynamic Duo of Cyclodextrins and Gene Delivery (40 min*)
    Milo Malanga, CarboHyde
  • Unlock the potential of KLEPTOSE® Hydroxypropyl beta-cyclodextrin in biologics downstream process and formulation development (40 min*)
    Peng Tao, BioPharma Research Manager, Roquette
  • Polysorbates versus KLEPTOSE® HPB Hydroxypropyl Beta-Cyclodextrin: Comparative Study on Stability & Antibody Stabilization (40  min*)
    Hailong Zhang, Research Analytical Manager, Roquette
  • Panel discussion (45 min): Cyclodextrins-based formulations in Biopharma – current and future applications, advantages, and challenges

See more details here: Webinar: Cyclodextrins in Biopharma | Roquette

Roquette announces strategic investment and innovation agreement with Beren Therapeutics P.B.C.

carbohydrates, drug development

Roquette, a leading provider of pharmaceutical excipients and global leader in plant-based ingredients, announced a strategic investment with Beren Therapeutics and the launch of an innovation agreement to expand the full potential of Beren’s cyclodextrin technologies and their medicinal applications. 
These collaborations among key players are vital to advance cyclodextrin-based innovations and to bring bright ideas closed to the market.
Way to go, guys!

Original press release here!

2-Hydroxypropyl-β-cyclodextrin (HPβCD) as a Potential Therapeutic Agent for Breast Cancer

Today's cyclodextrin,

today’s cyclodextrin:
Breast cancer is a global burden with the most severe subtype being triple-negative breast cancer (TNBC). Despite advances in conventional therapies, treatment for TNBC is currently lacking. Interestingly, cholesterol has gained interest as a potential therapeutic target due to cancer cells’ increased reliance on this macromolecule. Treatment with the cholesterol-depletory agent 2-hydroxypropyl-β-cyclodextrin (HPβCD) impeded the growth of cancer cells and further led to cancer cell death, which could be attributed to an altered cellular cholesterol profile following treatment. Furthermore, mice xenograft studies indicated complete eradication of early-stage tumours with no relapse, followed by a remarkable reduction in intermediate- and late-stage tumours, respectively. SFRP1 was identified as a possible molecular target facilitating the therapeutic action of HPβCD. These findings consequently potentiate cholesterol depletion as a novel anticancer strategy to be pursued.

University of the Witwatersrand – Tawanda Ziningav Reubina Wadee, Mandeep Kaur et al

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Renatus and Carbohyde sign MOU to co-develop novel cholesterol modulators for CNS disease applications.

news

By combining Renatus’ proprietary cholesterol modulator and Carbohyde’s expertise in medicinal chemistry, the agreement aims to derive novel cholesterol modulators with improved CNS delivery.

Carbohyde is a pharma company specialized in developing carbohydrate-based APIs led by experts in carbohydrate chemistry, analysis, and pharmaceutical development. The company’s primary focus is neurodegenerative diseases, yet they have various programs in various unmet medical indications. 

Renatus is specialized in developing cyclodextrin-based cholesterol modulators. The company’s chronic kidney disease program is currently in an IND-enabling stage, looking to complete the IND application by 2025. The company is developing pipelines for other cholesterol-driven diseases including CNS diseases.

 “We have been following the technology of Renatus for a long time and built this relationship brick-by-brick. Our philosophy is that we can achieve much more with joint efforts, and this partnership will bring out the best of each partner, I am sure” as Tamas Sohajda, a member of CarboHyde’s scientific board shared his views on this strategic collaboration.

“Our proprietary cyclodextrin exhibits a superior safety profile over hydroxypropyl beta-cyclodextrin, which is currently in clinical trials for several cholesterol-driven diseases. Ototoxicity is a dose-limiting toxicity of the clinical-stage cyclodextrin and leads to irreversible hearing loss. It can induce kidney injury in some cases. However, our cyclodextrin injected at higher doses failed to induce such toxicity. Besides safety, it has shown greater efficacy in normalizing cholesterol homeostasis in some of the cholesterol-associated disease models we are exploring. I am very pleased to work with Carbohyde. We have a lot in common and share a common vision. The collaboration will significantly promote the application of our cyclodextrin for CNS diseases wherein cholesterol is causing trouble,” said Heegon Kim, CEO of Renatus.

Oculis announces positive top-line results from diamond Stage 1 Phase 3 trial in diabetic macular edema with OCS-01 eye drops

drug delivery,

today’s #cyclodextrin:
Oculis, a global biopharmaceutical company purposefully driven to save sight and improve eye care, announced positive top line results from Stage 1 of its Phase 3 trial of OCS-01 (dexamethasone formulated in gamma-cyclodextrin #nanoparticles) eye drops in Diabetic Macular Edema (DME). DME is the leading cause of visual loss and legal blindness in patients with diabetes, affecting around 37 million people worldwide, with a significant number of patients left untreated due to a lack of convenient treatment options.
OCS-01, in this 3-month trial, has met both clinical efficacy endpoints (main BCVA change, proportion of patients with 3 lines gain) that are required for regulatory approval if met at 12 months treatment duration.

See the official annoucement here

The Role of Cyclodextrin in the Construction of Nanoplatforms: From Structure, Function and Application Perspectives

carbohydrates, drug delivery

The Role of Cyclodextrin in the Construction of Nanoplatforms: From Structure, Function and Application Perspectives
Drug delivery systems consisting of cyclodextrins (CyDs) have kept constant attention for good compatibility, negligible toxicity, and improved pharmacokinetics of drugs. The unique hollow structure has endowed a lot of functions, such as the inclusion of guest molecules, functional modification of active hydroxyl groups, and noncovalent interactions. Besides, the polyhydroxy structure has further extended the functions of CyDs by inter/intramolecular interactions and chemical modification. Furthermore, the versatile functions of the complex contribute to physicochemical characteristics alteration of the drugs, therapeutic talent, stimulus-responsive switch, self-assemble capability, and fiber formation. This review attempts to list the recent progress of CyDs and discuss their roles in the drug delivery system. Future perspectives of the construction of CyD-based drug delivery systems are also discussed at the end of this review, which may be the possible direction for the construction of more rational and cost-effective delivery vehicles.

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Antimony and naphthalene can be simultaneously leached from a combined contaminated soil using carboxymethyl-β-cyclodextrin as a biodegradable eluant

Egyéb kategória

today’s cyclodextrin:
The use of CDs in soil remediation has a long history. Here is the most recent chapter.
The removal efficiency of antimony (Sb) and naphthalene (Nap) from a combined contaminated soil was studied by carboxymethyl-β-cyclodextrin (CMCD) leaching and reveal its remediation mechanisms. The results show that the highest removal efficiencies of Sb and Nap were 94.82% and 93.59%, respectively. The breakthrough curves show that CMCD had a stronger inclusion capacity of Nap than Sb, and Sb could enhance the adsorption capacity of Nap, while Nap weakened the adsorption of Sb during CMCD leaching. CMCD is a good eluant for remediating soil contaminated by a combination of heavy metals and polycyclic aromatic hydrocarbons (PAHs), and its remediation mechanisms depend on the complexation reactions between the surface functional groups and inclusion reactions in the internal cavities.

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OKL-1111, A modified cyclodextrin as a potential universal reversal agent for anticoagulants

drug discovery,

The fantastic story of a novel cyclodextrin API.
Antithrombotic therapy is inevitably associated with a risk of bleeding and these bleeding complications can be life-threatening. Recently, specific reversal agents were developed for the direct factor Xa and thrombin inhibitors (DOACs). However, next to the fact that these agents are relatively expensive, the use of selective reversal agents complicates the treatment of bleeding patients in practice. A class of cyclodextrins with procoagulant properties was recently discovered. the lead compound being OKL-1111.
OKL-1111 concentration-dependently reversed the in vitro anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban in the thrombin generation assay. Also, in the absence of a DOAC, OKL-1111 concentration-dependently accelerated coagulation in this assay but did not initiate coagulation. The reversal effect was also seen for all DOACs in the rat tail cut bleeding model. In addition, when tested with other anticoagulants, OKL-1111 also reversed the anticoagulant effect of the vitamin K antagonist warfarin, the low molecular weight heparin enoxaparin, the pentasaccharide fondaparinux and the platelet inhibitor clopidogrel in vivo. OKL-1111 did not have prothrombotic effects in the Wessler model.

Alveron Pharma – Okklo Life Sciences – Sanquin
Joost Meijers, Kamran Bakhtiari, Alex Zwiers, Stephan Peters

See the full article here