P2a Open Label Study to Evaluate 2-HPβCD in Subjects With Diabetic Kidney Disease

Today’s cyclodextrin: After a long time, HPBCD will be evaluated again in clinics, now in a new application.
ZyVersa Therapeutics Inc. is sponsoring this Phase 2a open-label, two- to three-center study to evaluate the clinical efficacy and safety of one dose level of 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) given intravenously in adult patients with type 2 diabetes, diabetic kidney disease (DKD), and proteinuria.

According to the proposed mechanism of action, HPBCD entraps and passively removes intracellular cholesterol from the kidney. It is also believed to promote active cholesterol removal through up-regulation of cholesterol efflux transporters ABCA1 and ABCG1.

Study Details | P2a Open Label Study to Evaluate 2-HPβCD in Subjects With Diabetic Kidney Disease | ClinicalTrials.gov

Insulin formulation and methods of using same in preterm infants

Today’s cyclodextrin is an excellent example of using CDs (in this particular case, HPBCD) in peptide/protein formulations. ELGAN Pharma‘s patent concerns combining insulin, cyclodextrins, and other components, where the role of the CD is stabilization and cryopreservation.

As we see more examples of CD-protein combinations in research and clinical practice, I am convinced that this use will shape future applications.

Espacenet – US2024165205A1

Evaluating the Potential of Cyclodextrins in Reducing Aggregation of Antibody–Drug Conjugates with Different Payloads

Using cyclodextrins to prevent aggregation in protein formulations has been known for some time, and we have already published a lot about this topic.

This paper from Florian Johann, Steffen Wöll, and Henning Gieseler adds some special spice to the application as they investigate the potential of CDs in reducing aggregation of Antibody–Drug Conjugates with different payloads.

The main takeaways of the study are:

Hydroxypropylated (CDs) reduced agitation-induced aggregation in all tested ADCs without causing destabilization during incubation at 40 °C.

Native CDs that are not surface active partially reduced agitation-induced aggregation in ADCs, suggesting the possibility of stabilizing mechanisms beyond mere competition at the air-liquid interface.

ADC-specific formulation effects were observed, e.g., superior performance of the large HPγCD type in stabilizing a highly unstable ADC with a bulky fluorophore payload during incubation.

Evaluating the Potential of Cyclodextrins in Reducing Aggregation of Antibody–Drug Conjugates with Different Payloads – ScienceDirect

Long-Chain Alkylthio Cyclodextrin Derivatives for Modulation of Quorum-Sensing-Based Bioluminescence in Aliivibrio fischeri Model System

Today’s cyclodextrin paper by CarboHyde CSO Milo Malanga PhD, in collaboration with former colleagues from Cyclolab R&D Ltd. and Budapest University of Technology and Economics, sheds light on the potential of cyclodextrins to inhibit bacterial communication through quorum sensing.

Quorum sensing is vital for bacteria to coordinate activities, but inhibiting this process can be a game-changer in combating bacterial infectivity. Cyclodextrins encapsulate signal molecules, disrupting bacterial communication and, consequently, the expression of virulence factors.

Excitingly, our research shows that cyclodextrins exhibit a notable inhibitory effect on the quorum-sensing system of A. fischeri. The impact varies with alkyl chain length, with alkylthio substitution amplifying inhibition and quaternary ammonium groups mitigating it. These findings highlight cyclodextrins’ potential as a promising therapeutic avenue for treating bacterial infections.

IJMS | Free Full-Text | Long-Chain Alkylthio Cyclodextrin Derivatives for Modulation of Quorum-Sensing-Based Bioluminescence in Aliivibrio fischeri Model System (mdpi.com)

Using an effective amount of methyl-β-cyclodextrin as a combined auxiliary drug

Today’s cyclodextrin this recent patent of RemeGen Biosciences suggests that cyclodextrins, particularly methyl-beta-cyclodextrin (Fine Chemicals – www.carbohydesolutions.com) can significantly improve the efficacy of antibody-drug conjugates so that some of the ADC drugs with safety issues caused by excessive dosage can be developed. Moreover, due to the reduction in the dosage of ADC drugs, the cost of production and treatment for patients have also been significantly reduced, thereby being beneficial.

Espacenet – US2024189341A1

Lipid nanoparticles for nucleic acid delivery

Today’s cyclodextrin is this great patent from Roquette‘s team, Tao Peng, Lucas Goh, Jeff Chang Shih Chieh on a new class of Lipid nanoparticles (LNPs) that can be used for nucleic acid delivery, wherein LNPs comprise a nucleic acid and a nonionic or cationic cyclodextrin compound.

How do you see the future of CDs in gene therapy? Will we see solutions commercialized in the future? In GENEGUT we certainly work towards this goal!


Study of progesterone complexation in cyclodextrins and cyclodextrin-based nanosponges as an example of solvent-free complexation

Today’s cyclodextrin makes me feel proud as it is the first paper of your bright young chemist Daniel Bisericaru, sprouting from the intense and fruitful collaboration between Francesco Trotta‘s team and Adrián Matencio Durán at Università degli Studi di Torino and CarboHyde.

In this work and using kneading, we have compared the encapsulation of progesterone, a lipophilic hormone used in hormone replacement therapy, with β-CD and Nanosponges. The project opens the door to new medical formulations of progesterone, supporting the ball-milling kneading as an exciting way of making complexes.

cyclodextrin, progesteron

Wacker production site celebrates 25th Anniversary of manufacturing cyclodextrins

Today’s cyclodextrin is a small tribute to a huge contribution to the industrial cyclodextrin applications.

WACKER Chemical Corporation (WCC) established its Eddyville bioprocessing plant in 1999 and recently celebrated its 25th anniversary. The facility manufactures three different high-quality cyclodextrins: Alpha, Beta and Gamma. It is also the world’s sole commercial-scale manufacturer of Alpha and Gamma cyclodextrins.

Guided by WACKER’s global leadership, the Eddyville biotech facility has been at the forefront of cyclodextrin production since it was first built. The cyclodextrin products manufactured by WACKER became known worldwide under the trade names CAVASOL® and CAVAMAX®.

WACKER’s Eddyville Production Site Celebrates 25th Anniversary of Manufacturing Cyclodextrins for Global Customers (prnewswire.com)


GENEGUT meeting in Porto

Today’s #yclodextrin is about the fantastic progression of the GENEGUT project CarboHyde is part of.

The 5th in-person General Assembly meeting was kindly hosted by our partners at i3S – Instituto de Investigação e Inovação em SaúdeBruno SarmentoCatarina Leite Pereira in Porto, PT 🚀

We (Kristóf Felegyi) reported the chemistry work, which was our part, and now look forward to seeing how these building blocks will perform in RNA delivery and eventually in drug formulation. Caitriona O’Driscoll and Ana Francisca Soares presented some of the promising data at the 21st International Cyclodextrin Symposium last week.

We look forward to interesting discussions, progress updates and networking within the GENEGUT consortium 💡

GENEGUT, Porto, Horizon EUrope

β-cyclodextrin polymer as tetrodotoxins scavenger in oyster extracts

Today’s cyclodextrin is a fascinating example of how to use the scavenging capabilities of cyclodextrins to develop tools against natural toxins by Alex Fragoso’s team.

Tetrodotoxins (TTXs) are potent marine neurotoxins involved in humans’ poisoning cases after consuming some marine organisms. In this work, five insoluble cyclodextrin polymers with different chemical structures have been investigated as novel clean-up materials for oyster extracts containing TTXs.

The best recoveries have been achieved with βCDP-14-DS2 (∼100 %), which allowed exposing cells to 27-fold higher oyster matrix concentrations and decreased the LOQ down to 46 µg equiv. TTX/kg.

Then, the applicability of this strategy has been demonstrated with oyster extracts from The Netherlands and comparing the results with immunoassay and liquid chromatography-tandem mass spectrometry (LC-MS/MS). This clean-up strategy combined with CBA could be implemented for TTXs detection in monitoring programs to ensure seafood safety.

β-cyclodextrin polymer as tetrodotoxins scavenger in oyster extracts – ScienceDirect

cyclodextrin, CarboHyde