If it’s gene delivery and custom cyclodextrins – count us in!

drug discovery,

In this study – differing from the GENEGUT concept – our CSO, Milo Malanga PhD, designed cyclodextrin polymers that can form nanoplexes with various oligonucleotides due to their cationic nature. The we compared them with a standard polymer in the field: polyethylenimine.

QABCDPS exhibited lower toxicity compared to PEI, effectively binding both siRNA and mRNA and delivering them into vesicles in the cytoplasm, but showing different internalization patterns.

Polyplexes formed with PEI showed stronger biological effect than those with QABCDPS, which can be attributed to the strength of interactions facilitated by the polymers.

We hope to continue the collaboration with University of Debrecen – especially Ágnes Rusznyák and Ferenc Fenyvesi and design more efficient shuttles for the next round.

Comparison of the siRNA and mRNA Carrying Capacity of Quaternary Ammonium β-Cyclodextrin Polymer and Polyethylenimine

pharmaceutics-18-00713Download

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

Today's cyclodextrin, drug discovery,

What can we bring out of cyclodextrin polymers at CarboHyde?

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

Cyclodextrins in diabetic wound healing

Today's cyclodextrin, drug discovery,

Using CDs for wound healing has been in the spotlight for a long time, many applications and promising prototypes were developed, yet none reached the market.

This may change with the innovation of Jun Li at National University of Singapore who made a smart multifunctional ROS-responsive supramolecular hydrogel.

The polymer is dynamically crosslinked by inclusion complexes of β-cyclodextrin (βCD) and ferrocene (Fc).

This hydrogel facilitates the on-demand release of interleukin-4 (IL-4) while exhibiting intrinsic antibacterial properties.

The system subsequently reprograms macrophages from the proinflammatory M1 phenotype to the anti‒inflammatory M2 phenotype, thereby addressing immune dysregulation in diabetic wounds.

The composition significantly enhanced wound closure, collagen density, and angiogenesis while reducing proinflammatory cytokines (IL-6 and TNF-α) and increasing anti‒inflammatory cytokine IL-10 levels.

Smart multifunctional ROS-responsive supramolecular hydrogel for simultaneously regulating oxidative stress, immune dysregulation, and bacterial infection in diabetic wound healing – ScienceDirect

Another cyclodextrin innovation from Hungary!

drug discovery, Today's cyclodextrin,

Now our global player in Centrifugal Partition Chromatography (CPC), RotaChrom Technologies published about Scalable enantioseparation of rac-voriconazole.

Features?
– Batch CPC sets the baseline, intensified to cyclic continuous stacked-injection CPC.
– MDM CPC mode enables continuous injection and dual-outlet product collection.
– MDM CPC intensification delivers an overall ≈25× productivity gain vs resolution.
– Continuous CPC reduces solvent and selector use via repeated phase recycling.

And the best part?
The cyclodextrin, of course. To improve process economics, sulfobutyl ether-β-cyclodextrin (SBE-β-CD) was replaced with lower-cost randomly methylated β-cyclodextrin (RM-β-CD) without compromising the partitioning and selectivity required for MDM operation.

Continuous MDM CPC afforded (2R,3S)-voriconazole at ≥99.8% optical purity and 99.9% enantiomeric excess (ee), with 81% isolated yield

Congrats to Anita Kiss, Dóra Rutterschmid, Szabolcs Muráth!

Formulation of cyclodextrins?

Today's cyclodextrin, drug discovery

They go (adeno) viral!

1. What Cyclodextrin Brings to Adenoviral Formulations
Hydroxypropyl-β-cyclodextrin (HPβCD) helps stabilize adenoviral vectors by creating a protective environment around the particles, reducing aggregation and degradation.

2. Supporting Complex Purification Workflows
After multi-step purification—such as tangential flow filtration and two-step anion exchange chromatography—cyclodextrin helps maintain the integrity of the highly purified recombinant adenovirus.

3. Enhancing Stability in the Final Drug Product
In the final formulation buffer, HPβCD works alongside excipients like glycerol, sucrose, and polysorbate 80 to improve thermal and storage stability, helping the therapy remain potent over time.

4. Enabling Reliable Delivery of Gene Therapies
By protecting the viral capsid and improving overall formulation robustness, cyclodextrin plays a quiet but vital role in ensuring adenoviral gene therapies reach patients in their intended, effective form.

Minna Hassinen – Ferring Pharmaceuticals – congratulations on the fantastic work!

Espacenet – METHOD FOR THE PURIFICATION OF RECOMBINANT ADENOVIRUS VECTORS

Want to play with Sugammadex in AR?

drug discovery, news,

We are happy to share this little beta version game that Balázs Attila Kondoros and Kristóf Felegyi put together during their Bicyclos HEurope secondment. Special thanks for the support and guidance of Angel Piñeiro and Rebeca Garcia-Fandino for their amazing work.

Molvelle AR Software was developed within the framework of the European Bicyclos project (EC-funded Staff Exchange project n° 101130235) in collaboration with the University of Santiago de Compostela, MD.USE Innovative Solutions S.L., Carbohyde, and IES Rosalía de Castro, Santiago de Compostela.

Enjoy!

Molvelle Ar en App Store

Supersaturated Drug Delivery System of Oxyberberine Based on Cyclodextrin Nanoaggregates: Preparation, Characterization, and in vivo Application

drug discovery, Today's cyclodextrin,

Today’s cyclodextrin is a fascinating practical application of CDs – how can we create a supersatured drug delivery system (SDDS)?

In this paper, Oxyberberine (OBB) – hydroxypropyl-β-CD SDDS was prepared using the ultrasonic-solvent evaporation method.

The oral relative bioavailability of OBB-HP-β-CD SDDS was also 16 times enhanced compared to that of the raw material. Finally, an in vivo pharmacodynamic assay showed that the anti-hyperuricemic potency of OBB-HP-β-CD SDDS was approximately 5– 10 times higher than that of OBB raw material.

Supersaturated drug delivery system of oxyberberine | IJN (dovepress.com)

CarboHyde blog, Supersaturated Drug Delivery System of Oxyberberine Based on Cyclodextrin Nanoaggregates: Preparation, Characterization, and in vivo Application

FDA-Approved Alzheimer’s Medications

drug development, drug discovery, , ,

⚫ Alzheimer’s disease takes a toll on not just the people suffering from the disease but also on their loved ones and caregivers in a way that almost no other illness does.

⚫ The Alzheimer’s disease market is projected to experience robust growth at a compound annual growth rate of 20% from $2.2 billion in 2020 to $13.7 billion in 2030!

🔶 Drug Development Pipeline:
🔸 187 current trials assessing 141 unique drugs
🔸 Phase 3: 36 drugs
🔸 Phase 2: 87 drugs
🔸 Phase 1: 31 drugs

🔷 Phase 3 has 36 agents in 55 trials:
🔹 DMT*-Biologics: 9 (25%)
🔹 DMT*-Small molecules: 15 (42%)
🔹 Putative cognitive-enhancers: 5 (14%)
🔹 Neuropsychiatric symptoms: 7 (19%)
*DMT stands for disease-modifying therapies

🔶 Most Common Targets:
🔸 Transmitter receptors, amyloid, synaptic function, and inflammation

🔷 58 new drugs have entered the pipeline in the past year!
🔷 28% of candidate therapies are repurposed from other diseases!

⚫Despite the hype, controversy, and occasional scandal surrounding the approval of Alzheimer’s drugs, and the disappointing reports of the ineffectiveness of recently approved drugs, many companies are still dedicating time and resources to finding a potential cure for this debilitating disease. This gives hope that the future is bright for those living with Alzheimer’s.

🔶 Learn more:
🔸 Alzheimer’s disease drug development pipeline: 2023 – Cummings – 2023 – Alzheimer’s & Dementia: Translational Research & Clinical Interventions – Wiley Online Library
🔸 Alzheimer’s Drug Market To Hit $13B As FDA Approvals And Insurance Coverage Escalate (forbes.com)

Great collection from Maryam Daneshpour

Sustained Delivery of Cu(II)-Based DNA Intercalators by Nanometer-Sized Cyclodextrin-Based Porous Polymers

drug discovery, , ,

Apparently, cyclodextrin-based oligonucleotide delivery is becoming a hot research topic. This recent study from University of Nova Gorica – Tina Škorjanc, PhD, Damjan Makuc, Nora Kulak, and Valant Matjaz presents a cyclodextrin porous polymer to form nanometer-sized particles and used as a delivery vehicle for metal-free and Cu(II)-metalated anthraquinone-based DNA intercalators.

Sustained Delivery of Cu(II)-Based DNA Intercalators by Nanometer-Sized Cyclodextrin-Based Porous Polymers | ACS Applied Nano Materials