The Story Behind Sugammadex’s Success

Few medical breakthroughs have been as transformative as Sugammadex. This remarkable drug, developed by the Dutch pharmaceutical company Organon, represents a significant milestone in anesthesia management, particularly in reversing the effects of neuromuscular blockade.

The journey of Sugammadex began with the quest to address the limitations of traditional methods for reversing muscle relaxation induced by anesthesia. These methods often involve lengthy processes with unpredictable outcomes and potential side effects. Recognizing the need for a safer, more efficient solution, researchers turned their attention to cyclodextrins.

Cyclodextrins are a family of cyclic oligosaccharides characterized by a hydrophobic interior and a hydrophilic exterior. Their unique structure enables them to encapsulate guest molecules, forming inclusion complexes. This property intrigued scientists, leading to the exploration of cyclodextrins as potential candidates for reversing neuromuscular blockade.

Among cyclodextrins, gamma-cyclodextrin emerged as a promising candidate due to its ability to encapsulate the neuromuscular blocking agents rocuronium and vecuronium. Building upon this discovery, Organon researchers synthesized Sugammadex, a modified gamma-cyclodextrin specifically designed to encapsulate rocuronium and vecuronium with high affinity.

The first occurrence of Sugammadex in the scientific literature can be traced back to a pivotal study published in 2001. This groundbreaking research, titled “Org 25969, a Novel, Specific Reversal Agent for Rocuronium-Induced Neuromuscular Blockade,” was conducted by researchers from Organon, the pharmaceutical company that developed Sugammadex.

In this study, the authors introduced Sugammadex, then known as Org 25969, as a novel reversal agent for rocuronium-induced neuromuscular blockade. They demonstrated its efficacy in rapidly and effectively reversing the effects of rocuronium, a commonly used neuromuscular blocking agent during anesthesia. This publication laid the foundation for subsequent research and clinical trials that ultimately led to the approval and widespread adoption of Sugammadex as a critical tool in anesthesia management.

Since its initial introduction in scientific literature, Sugammadex has been the subject of numerous studies, reviews, and clinical trials, further validating its efficacy and safety in clinical practice. Its discovery marked a significant advancement in anesthesia pharmacology and continues to benefit patients undergoing surgical procedures worldwide.

The development of Sugammadex was not without challenges. Regulatory hurdles and safety concerns necessitated extensive testing and refinement. However, the perseverance of the research team eventually paid off, culminating in the approval of Sugammadex for clinical use in various countries.

The impact of Sugammadex on anesthesia practice cannot be overstated. Its rapid and reliable reversal of neuromuscular blockade offers numerous advantages, including shorter recovery times, improved patient safety, and enhanced control for medical professionals. By streamlining procedures and minimizing risks, Sugammadex has revolutionized anesthesia management, setting a new standard of care in the field. Currently, it is a blockbuster drug marketed by MSD and developed by dozens of generic companies.

In summary, Sugammadex represents the convergence of scientific ingenuity, perseverance, and innovation. Its development underscores the pivotal role of cyclodextrins in drug discovery and highlights the transformative potential of research-driven solutions in improving patient outcomes.

Would you like to learn more? Here are some great sources to start with!

Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block

Preclinical pharmacology of sugammadex

EMA submission document

Sugammadex – A revolutionary drug in neuromuscular pharmacology

Isosorbide mononitrate spray and preparation method

Today’s cyclodextrin is an innovative formulation of isosorbide mononitrate. In this patent, a cyclodextrin complex is prepared, suitable to develop sprays, having the advantages of quick response, small irritation, and convenience in use.

Isosorbide mononitrate is a medication primarily used for the prevention of angina pectoris, which is chest pain caused by reduced blood flow to the heart. It works by relaxing and widening blood vessels, which allows more blood and oxygen to reach the heart, thereby reducing the heart’s workload and helping to prevent episodes of chest pain. It belongs to a class of drugs known as nitrates.

Isosorbide mononitrate is used in a long-acting form, which is not suitable for relieving an acute angina attack but is used regularly to decrease the frequency and severity of angina episodes. It may also be used in other conditions as determined by a doctor, based on its vascular effects.

It is typically available in tablet form for oral administration. This medication is taken by mouth and is formulated as either immediate-release or extended-release tablets, depending on the intended dosing schedule and therapeutic need. The drug acts by releasing nitric oxide, which helps to relax and widen blood vessels, but the drug itself is solid in its delivery form.

Espacenet – Isosorbide mononitrate spray and preparation method thereof

Monitoring the conformational ensemble and lipid environment of a mechanosensitive channel under cyclodextrin-induced membrane tension

Today’s cyclodextrin from Christos Pliotas form The University of Manchester research reveals new insights into the activation kinetics of mechanosensitive channels. By mimicking tension through the sequestering of lipids from membranes, cyclodextrins enable the conversion of mechanical cues into electrical signals. The extent of MscS activation depends on the cyclodextrin-to-lipid ratio, with lipids being depleted slower when MscS is present.

This has implications for the activation kinetics of MscS in different membrane scaffolds. Additionally, MscS transits from closed to sub-conducting state(s) before it desensitizes due to the lack of lipid availability in its vicinity required for closure.

This approach allows for monitoring tension-sensitive states in membrane proteins and screening molecules capable of inducing molecular tension in bilayers.

Monitoring the conformational ensemble and lipid environment of a mechanosensitive channel under cyclodextrin-induced membrane tension: Structure (cell.com)

Development of Broad-spectrum β-cyclodextrins-Based Nanomaterials Against Influenza Viruses

Cyclodextrins as antivirals? Why not?

Caroline Tapparel VuFrancesco Stellacci and colleagues from EPFL and University of Geneva created a groundbreaking molecule, CD-SA, that mimics flu virus receptors to fight off multiple influenza strains effectively! 🦠💥 Our studies show CD-SA outperforms existing treatments like Oseltamivir, offering a new hope against flu with fewer chances of resistance when coupled with IFN λ1. Exciting results from lab to mice models prove its potent antiviral powers! 🚀🔬


Development of Broad-spectrum β-cyclodextrins-Based Nanomaterials Against Influenza Viruses | bioRxiv

Multifunctionality of cyclodextrin-based polymeric nanoparticulate delivery systems for chemotherapeutics, combination therapy, and theranostics

As cancer remains one of the most challenging diseases to treat, scientists have developed various medications and therapeutic approaches to combat it. To protect drugs from degradation or inactivation, efficient delivery systems are required during administration. In this context, cyclodextrin-based polymeric nanosystems have emerged as an effective treatment approach against cancer.

Cyclodextrins are natural oligosaccharides that can trap water-insoluble molecules inside their hydrophobic core, making them valuable in pharmaceutical research. When combined with polymeric nanoparticles, CD-based delivery systems provide versatile and tunable profiles, thanks to the submicron-sized PNPs. Recent studies have shown that CD-based delivery systems can successfully be applied in combination therapy and theranostics, providing multifunctional advantages against cancer.

The article by Lakshmi Sathi DeviCristina CasadidioMaria Rosa GigliobiancoPiera Di Martino and Roberta Censi from University of Camerino further discusses different binding approaches, release mechanisms of CD-drug complexation, and characterization studies. Promoting CD to a polymeric and nanoscale has demonstrated improved tumor targeting, reduced side effects, and prolonged drug release in preclinical studies and clinical trials. Notably, CD-based delivery systems, including CALAA-01, CRLX101, and CRLX301, have shown promising results in treating cancer.

Overall, cyclodextrin-based polymeric nanosystems hold great potential in tackling the abnormalities behind cancer by providing an efficient drug delivery system.

Multifunctionality of cyclodextrin-based polymeric nanoparticulate delivery systems for chemotherapeutics, combination therapy, and theranostics – ScienceDirect


Mirror-image cyclodextrins

today’s cyclodextrin:
Do you often take a good look in the mirror?

Nobel laureate Sir Fraser Stoddard, Daniel W. Armstrong, and their team report the syntheses of three mirror-image CDs—namely, α-, β- and γ-L-CDs, which are composed of six, seven and eight α-1,4-linked L-glucopyranosyl residues, respectively.

The availability of L-CDs has enabled the elucidation of an unprecedented chiral self-sorting of a racemic modification of β-CDs in the solid state and an investigation of the chiral recognition of enantiomeric fenchone by α-L-CD. This research identifies a missing piece of the cyclodextrin jigsaw and sets the stage for scientists to explore the mirror-image world of naturally occurring CDs.

Mirror-image cyclodextrins | Nature Synthesis

2024’s New FDA Drug Approvals


🌟 Discover the latest from the FDA’s CDER: 9 innovative drugs for Q1!
🧴Berdazimer (Zelsuvmi) tackles topical molluscum contagiosum with nitric oxide release.
💉Cefepime/enmetazobactam (Exblifep) combines forces for urinary tract infection relief.
💉LetibotulinumtoxinA (Letybo) smooths glabellar lines with botulinum neurotoxin.
💉Tislelizumab (Tivembra) fights esophageal squamous cell carcinoma with PD-1 mAb technology.
💊Resmetirom (Rezdiffra), a thyroid hormone receptor beta agonist, battles nonalcoholic steatohepatitis.
💊Aprocitentan (Tryvio) manages hypertension through endothelin receptor antagonism.
💊Givinostat (Duvyzat) aims at Duchenne muscular dystrophy with HDAC inhibition.
💉Sotatercept (Winrevair), an activin inhibitor, offers hope for pulmonary arterial hypertension patients.
💊Vadadustat (Vafseo) addresses CKD-related anemia in dialysis patients as an oral HIF-PH inhibitor.

Explore these groundbreaking treatments! Our appreciation to Chris De Savi for the great compilation!

METHOD FOR THE PRODUCTION OF LARGE-RING CYCLODEXTRINS

Today’s cyclodextrin is a great patent on unusual CDs: large-ringed ones. The systematic experimental study of the properties of the large-ring cyclodextrins (LR-CDs) as host systems was hampered for a long time by the inability to obtain individual LR-CDs in quantities necessary for experimental examinations. Breakthrough in the situation was a recent patent and reports of Sophie Beeren and coworkers from DTU – Technical University of Denmark

Now we have a scalable method, and the isolation of the product does not require chromatography. And what should we do with these CDs? Let’s start by looking into analytical, biotech, and pharma applications. Then we shall see…

WO2024042228 METHOD FOR THE PRODUCTION OF LARGE-RING CYCLODEXTRINS (wipo.int)

Induction of Exocytosis Rescues Lysosomal GM2 Accumulation in Tay-Sachs Disease

Tay-Sachs disease, a progressive neurodegenerative disorder caused by mutations in the HEXA gene, lacks effective treatment. This study explores the therapeutic potential of δ-tocopherol and hydroxypropyl-β-cyclodextrin, targeting lysosomal exocytosis in Tay-Sachs models. Results indicate significant lysosomal GM2 reduction, offering hope for future treatments.

Induction of Exocytosis Rescues Lysosomal GM2 Accumulation in Tay-Sachs Disease (hindawi.com)

Methods for the treatment of chronic kidney disease

We are happy to announce the acceptance of a great patent from CarboHyde’s collaborator, Renatus, a pharmaceutical company focused on developing cyclodextrin-based cholesterol metabolism modulators. Renatus is a pharmaceutical company whose mission is to provide safe and effective treatment options for the treatment of numerous cholesterol-driven diseases such as chronic kidney disease, atherosclerosis, and Alzheimer’s diseases. The core technology of the company allows the normalization of cholesterol homeostasis by removal of excessive and toxic cholesterol within diseased cells without significant harmful effects on normal cells.

The lead asset RN-005 is a cholesterol metabolism modulator that has proven strong therapeutic efficacy in preclinical models of both diabetic kidney disease (DKD) and focal segmental glomerulosclerosis (FSGS) wherein dysregulated cholesterol metabolism causes progressive damage and loss of function in the kidney. The gamma-cyclodextrin oligomers are effective in cholesterol metabolism enhancement, cholesterol efflux, reducing inflammatory cytokine secretion, renal clearance of cholesterol, and/or reducing albuminuria. Therefore, the gamma-cyclodextrin oligomers can be used to treat or alleviate chronic kidney disease, symptoms thereof and/or complications related to chronic kidney disease.

Espacenet – METHODS FOR THE TREATMENT OF CHRONIC KIDNEY DISEASE