Exceptional stability of the sugammadex-solasodine complex: Insights from experimental and theoretical studies

drug development

A new paper out!

Sugammadex (SGM) is the first cyclodextrin (CD)-based selective relaxant binding agent. We investigated its ability to capture natural aminosteroid phytotoxins, and assessed its potential as an antidote for intoxication.

SGM significantly increased cell survival and reduced Solasodine (the toxic alkaloid chosen as model compound) toxicity in mHippoE-14 mouse hippocampal embryonic cells, supporting the hypothesis that SGM could act as an antidote to SS’s toxic effects.

Special thanks for the fantastic teamwork:
Eszter Kalydi – Semmelweis University
Fanni Sebák, Éva Moussong József Kardos, Andrea Bodor Szabolcs Béni – Eötvös Loránd University
Béla Fiser – University of Miskolc
Babak Minofar – University of Lodz
Milo Malanga PhD – CarboHyde

Exceptional stability of the sugammadex-solasodine complex: Insights from experimental and theoretical studies – ScienceDirect

Formulation and investigation of differently charged β-cyclodextrin-based meloxicam potassium containing nasal powders

drug development, Today's cyclodextrin

Today’s cyclodextrin is a nice formulation study from one of the best Hungarian pharmaceutical universities, the University of Szeged, who study various excipients – CDs among others – that have an important role in nasal formulations to increase the permeability of the mucosa and prolong the residence time of the drug.

The charged cyclodextrin-based formulations showed significantly higher adhesive force values regardless of the presence of PVA. The drug release was fast and complete, and the permeation of meloxicam was enhanced.

Patricia Varga, Anett Németh, Scarlett Zeiringer, Eva Roblegg, Budai-Szűcs Mária, Csilla Balla-Bartos, Rita Ambrus

Formulation and investigation of differently charged β-cyclodextrin-based meloxicam potassium containing nasal powders – ScienceDirect

Enhancing Oral Drug Absorption: Overcoming Physiological and Pharmaceutical Barriers for Improved Bioavailability

drug development, Today's cyclodextrin

Enhancing Oral Drug Absorption

is the ultimate goal of using cyclodextrins. This great paper shows how Physiological and Pharmaceutical Barriers can be overcome for Improved Bioavailability.
Rashmi Maurya, Akash Vikal, Dr. Preeti Patel, Raj Kumar, & Dr. Balak Das Kurmi

“Enhancing Oral Drug Absorption: Overcoming Physiological and Pharmaceutical Barriers for Improved Bioavailability” | AAPS PharmSciTech (springer.com)

The application of cyclodextrins in drug solubilization and stabilization of nanoparticles for drug delivery and biomedical applications

carbohydrates, drug delivery, drug development

Not many things get better with years passing but some do.
Things like:
– whiskey,
– wine
– blue jeans
– friendships
and Thorsteinn Loftsson

This was my first thought when reading this paper, which I coauthored with Hay Man Saung Hnin Soe and Phatsawee Jansook on cyclodextrin-based nanoparticles.

This review emphasizes the role of cyclodextrins (CDs) in stabilizing colloidal nanoparticles (NPs) and improving drug solubility. The integration of CDs with NPs offers a synergistic strategy that enhances drug delivery and expands the scope of biomedical applications. Furthermore, the review thoroughly explores the potential of CDs to boost the stability and therapeutic effectiveness of colloidal NPs, positioning them as promising candidates for advanced drug delivery systems

The application of cyclodextrins in drug solubilization and stabilization of nanoparticles for drug delivery and biomedical applications – ScienceDirect

Encapsulation of 5-fluorouracil in cholesteryl-modified cyclodextrin: thermal, spectral, and computational assessment of drug inclusion efficiency

drug development, Today's cyclodextrin

Today’s cyclodextrin:
I have seen many visualizations and artwork of cyclodextrins so far, yet this “jellyfish” cover caught my eye.

Cholesteryl-modified cyclodextrin (also a great idea) to capture and deliver 5-fluorouracil.

Encapsulation of 5-fluorouracil in cholesteryl-modified cyclodextrin: thermal, spectral, and computational assessment of drug inclusion efficiency – Journal of Materials Chemistry B (RSC Publishing)

Axsome Therapeutics Announces FDA Acceptance of NDA Resubmission for AXS-07 for the Acute Treatment of Migraine

drug development, Today's cyclodextrin

Today’s cyclodextrin update brings news of the 2nd oral drug to be marketed using sulfobutylether-beta-CD.

Axsome Therapeutics, Inc. has announced that the U.S. FDA has acknowledged the resubmission of the NDA for AXS-07, an oral, rapidly absorbed, multi-mechanistic investigational medicine for the acute treatment of migraine. AXS-07 combines MoSEIC™ meloxicam and rizatriptan, offering a new molecular entity for migraine treatment enabled by Axsome’s innovative technology.

About Migraine
Migraine is a serious neurological condition characterized by recurrent attacks of pulsating, often severe and disabling head pain associated with nausea, sensitivity to light, and sensitivity to sound. An estimated 39 million Americans suffer from migraine, and it is the leading cause of disability among neurological disorders in the United States according to the American Migraine Foundation. Published surveys of migraine sufferers found that more than 70% are not fully satisfied with their current treatment and desire therapies that work faster, more consistently, and result in less symptom recurrence.

About AXS-07
AXS-07 is a novel, oral, rapidly absorbed, multi-mechanistic investigational medicine for the acute treatment of migraine, consisting of MoSEIC™ meloxicam and rizatriptan. Meloxicam is a new molecular entity for migraine enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which results in rapid absorption of meloxicam while maintaining a long plasma half-life. Meloxicam is a COX-2 preferential non-steroidal anti-inflammatory drug and rizatriptan is a 5-HT1B/1D agonist. AXS-07 is designed to provide rapid, enhanced and consistent relief of migraine, with reduced symptom recurrence. AXS-07 is covered by more than 200 issued U.S. and international patents which provide protection until at least 2038. AXS-07 is not approved by the FDA.

Axsome Therapeutics Announces FDA Acceptance of NDA Resubmission for AXS-07 for the Acute Treatment of Migraine | Axsome Therapeutics, Inc. (gcs-web.com)

World-first lung cancer vaccine trials launched across seven countries

drug development

Doctors have begun trialing the world’s first mRNA lung cancer vaccine in patients, as experts hailed its “groundbreaking” potential to save thousands of lives.

The phase 1 clinical trial, the first human study of BNT116, has launched across 34 research sites in seven countries: the UK, US, Germany, Hungary, Poland, Spain and Turkey.

As a company working on drug delivery solutions for oligonucleotides, we hold our breath and watch carefully how this goes.

World-first lung cancer vaccine trials launched across seven countries | Lung cancer | The Guardian

Fascinating taste-masking matryoshka doll drug delivery systems are proposed by Bayer

drug development

The compositions comprise an active pharmaceutical ingredient and the multi-component taste-masking physical barrier comprising one or more of an ion exchange resin, a cyclodextrin, and a hydrocolloid. The patent: WO2024159161 TASTE-MASKING WITH A MULTI-COMPONENT PHYSICAL BARRIER (wipo.int)
BRADLEY, Reginald
Debanjan (Deb) Das
MEISEL, Gerald
Tejas Kekatpure

If you are interested in creating similar solutions with cyclodextrins, here you can learn more: Formulation development – www.carbohydesolutions.com



Insulin formulation and methods of using same in preterm infants

drug development, Today's cyclodextrin,

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

drug development, Today's cyclodextrin

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