What can we bring out of cyclodextrin polymers at CarboHyde?

Today's cyclodextrin, drug development, ,

Whatever you want, apparently 🙂

Our long-term collaboration with Salvo Sortino‘s team and Szabolcs Béni just yielded another great paper with Milo Malanga.

Here, we made a photoresponsive β-cyclodextrin branched polymer, where excitation of the Poly-βCD1 with visible blue light results in the generation of nitric oxide.

The negligible cytotoxic action of DOX, used well below the therapeutic doses, alone or in combination with the polymer in the dark, is enhanced in both cell lines under light irradiation exclusively when the drug is combined with Poly-βCD1 as a result of the combined action of NO.

Phototherapeutic β-Cyclodextrin-Branched Polymer Releasing Nitric Oxide with Fluorescent Self-Reporting and Its Combination with Doxorubicin | Biomacromolecules

Check out how CarboHyde cyclodextrin polymers worked in delivery!

Today's cyclodextrin, drug development,

Glioblastoma (GB) is the most common and aggressive malignant brain tumor, with a median survival of only 12–15 months.

Alternative therapeutic strategies—such as targeting the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway with MEK inhibitors like trametinib and selumetinib—are being explored.

However, their clinical success is currently hindered by inadequate delivery across the blood–brain barrier and dose-limiting toxicity.

In this work, Noemi Bognanni, Graziella Vecchio and colleagues investigate two cationic CyD polymers as potential nanocarriers for GB therapy based on trametinib and selumetinib.

Their multivalent architecture and positive charge can facilitate both the encapsulation of drugs and membrane interactions.

Positively Charged Polymers Based on Cyclodextrins for Trametinib and Selumetinib Delivery in Glioblastoma Cancer – Bognanni – 2026 – ChemMedChem – Wiley Online Library

Uses of cyclodextrin polymers.

Today's cyclodextrin, drug development

How about a case study now?From bacterial toxin to long-acting pain relief

Challenge: Chronic & neuropathic pain still largely rely on short-acting, addictive opioids.

Innovation: A β-cyclodextrin polymer that encapsulates mycolactone, turning an insoluble, UV-sensitive molecule into a stable, aqueous formulation.

Chemistry: Crosslinked β-CD forms multiple host–guest cavities, solubilising and protecting mycolactone without organic solvents.

Impact: In vivo, the pCD–mycolactone combo delivers strong, long-lasting analgesia from a single injection — a promising non-opioid alternative for difficult-to-treat pain.

Check out the patent in comments if you like the idea of Ruxandra Gref; Isabelle Marsollier and Estelle Marion. We do so!

Espacenet – LONG-ACTING PAIN-RELIEF FORMULATION

Would you like to design a similar polymer for you application? Let us know, we can help.

Sugammadex – Alfaxalone?

drug development,

Present: Sugammadex can be used to reverse rocuronium and similar NMBA.
The future: Alfaxalone?

This rat study shows that Sugammadex can reverse the anesthetic effects of alfaxalone.

Recovery speed from alfaxalone anesthesia is dependent upon sugammadex dose and sex.

Obviously, its not working as well as for the original target (Compared to saline controls, sugammadex shortened recovery times by 40%–60% following anesthesia induction) but the repurposing idea is nice.

What do you think? Can a scavenger like this be repurposed for other applications?

Use of Sugammadex to Reverse Alfaxalone Anesthesia in Rats – ScienceDirect

Enantioselective Complexation of Xylopinine: A Cyclodextrin-Assisted CE and NMR Study

Today's cyclodextrin, drug development, ,

Xylopinine (XPN) a natural cytotoxic, antimicrobial, and antimalarial compound
fits cyclodextrins well!

Milo Malanga PhD‘s latest collaboration with Semmelweis University (Erzsébet Várnagy, Fejős Ida, Tóth Gergő) and Eötvös Loránd University (Szabolcs Béni) shares insights into the encapsulation behavior:

Some cyclodextrins like subetadex provide excellent enantiomer resolution and could be key agents for quality control.

Enantioselective Complexation of Xylopinine: A Cyclodextrin-Assisted CE and NMR Study

Hydroxypropyl-Beta-Cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication

Today's cyclodextrin, drug development,


This study brings some fascinating highlights:

1. HP-BCD impacts cellular ACE2 distribution and early SARS-CoV-2 replication.

2. HP-BCD alters cholesterol and lipid droplets content and organization.

3. HP-BCD impairs viral compartments formation in SARS-CoV-2-infected cells.

4. HP-BCD affects both early and late stages of SARS-CoV-2 replication.

5. HP-BCD inhibition of SARS-CoV-2 is partially reversed by cholesterol replenishment.

Which do you think is the most impactful?

Hydroxypropyl-Beta-Cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication by modulating intracellular lipid dynamics and preventing viral replication complex formation – ScienceDirect

No cholesterol – no pain?

Today's cyclodextrin, drug development,

Let’s start the week with an amazing Hungarian paper from University of Pécs.

Cyclodextrin (CD) derivatives deplete cholesterol from membrane rafts in TRPV1 and TRPA1 channels, reducing receptor activation in vitro, anticipating in vivo analgesic effects.

The tested CD derivatives are promising agents for exerting peripheral analgesia and anti-inflammation via cholesterol depletion, also supported by in vitro and in silico findings.

Andrea Nehr-Majoros, Maja Payrits, Noémi Bencze, GYORGY SETALO JR, Rita Börzsei, Csaba Hetényi, Zsuzsanna Helyes, Éva Szőke

Cyclodextrins inhibit TRPV1 and TRPA1 activation-induced nociception via cholesterol depletion – Journal of Lipid Research

Selective removal of 7-ketocholesterol by a novel atherosclerosis therapeutic candidate reverts foam cells to a macrophage-like phenotype

Today's cyclodextrin, drug development,

Today’s cyclodextrin:

Say hello to Cyclarity Therapeutics‘s UDP-003, a promising new therapeutic that goes beyond managing atherosclerosis — it aims to reverse it by targeting one of its nastiest culprits: 7-ketocholesterol (7KC), a toxic oxidized form of cholesterol. 🧨🧬

Here’s what the science says:
🧼 UDP-003 selectively removes 7KC, a molecule notorious for turning immune cells into dysfunctional foam cells — the building blocks of atherosclerotic plaque
🔄 By clearing out 7KC, foam cells regain their phagocytic power and reduce harmful features like oxidative stress and lipid accumulation
🧲 The treatment downregulates CD47, a “don’t eat me” signal, and restores efferocytosis, helping clean up dead cells in plaques
🚽 7KC is not just neutralized — it’s flushed out via urine, suggesting effective systemic detox
✅ Preclinical safety looks good, and a Phase 1 clinical trial is already underway!

💡 Bottom line: By targeting the molecular root — not just the symptoms — of atherosclerosis, UDP-003 could become the first truly disease-modifying therapy for this global cardiovascular killer 🛡️❤️

Selective removal of 7-ketocholesterol by a novel atherosclerosis therapeutic candidate reverts foam cells to a macrophage-like phenotype – Atherosclerosis

HPBCD will be dosed in patients with diabetic kidney disease in Q2 2025

Today's cyclodextrin, drug development, ,

Today’s cyclodextrin:
ZyVersa Therapeutics Inc.‘ Cholesterol Efflux Mediator VAR 200 (HPBCD) will be dosed in patients with diabetic kidney disease in Q2 2025.

The first patient is expected to be treated in a phase 2a clinical trial in patients with DKD by the end of June of 2025. The intent of the study is to obtain renal patient proof-of-concept for VAR 200 prior to initiating a larger phase 2a/b for VAR 200’s lead indication, FSGS. The DKD study will evaluate VAR 200’s safety and efficacy (% change in proteinuria from baseline to week 12) in eight patients with type 2 diabetes who have diabetic kidney disease. This data will provide insights for designing the subsequent phase 2a/b FSGS study. The DKD study will be conducted at two clinical research sites.

I cannot wait to see how this goes!
ZyVersa Therapeutics Reports First Quarter 2025 Financial Results and Highlights Pipeline Progress :: ZyVersa Therapeutics, Inc.

Fascinating Hungarian invention in ophthalmic application

drug development,

After oral and parenteral formulation, ophthalmics are the 3rd most popular for cyclodextrin use.

Here is a fascinating Hungarian invention in the field of ophthalmology from Semmelweis University and University of Szeged.

US20250108034 EYE DROP FORMULATION

An ocular formulation comprising a cyclodextrin-formulated L-Ascorbic acid 6-palmitate (ASP), preferably for the treatment of fibrosis in the cornea, corneal haze, and wound.

Heartiest congratulations to György Tibor Balogh, PhD, DSc, dr. habil and his team and Gábor Katona, Ildiko Csoka and their team.

We hope to see many more of similar great solutions to come!