Cyclodextrin-Enabled Enantioselective Complexation Study of Cathinone Analogs

We have a nice read to propose for the week-started coffee, the most recent work of Szabolcs Béni from our advisory board and András DohárszkyFejős IdaEszter Kalydi and Gergely Völgyi.
A comprehensive investigation of the stability of cathinone derivatives and their cyclodextrin complexes.

Molecules | Free Full-Text | Cyclodextrin-Enabled Enantioselective Complexation Study of Cathinone Analogs (mdpi.com)

Educational material on cyclodextrins is available

In the past few years, we have created dozens of educational materials on various uses of cyclodextrin, such as complex preparation, monoclonal antibody formulation, uses in vaccines, gene therapy, and various non-pharma applications.

We collected these decks for you in two easy-to-digest platforms.

Here you can find (and download) the decks: https://www.carbohydesolutions.com/natures-gift-for-mankind-are-cyclodextrins/

On our YouTube channel, you can watch them as short videos:

https://www.youtube.com/@CarboHyde

Learn and enjoy!

Live Q&A on Cyclodextrins

Breaking News: Live LinkedIn Q&A Session on Cyclodextrins Unveils Insights from Industry Experts!

Join us for an exclusive live event on LinkedIn as we delve into the fascinating world of cyclodextrins! This dynamic Q&A session brings together industry experts, researchers, and enthusiasts to explore the diverse applications and cutting-edge advancements in the field of cyclodextrin science.

📅 Date & Time: January 23, 2024 14.00 CET

📍 Location: LinkedIn Live – https://www.linkedin.com/events/7150478953097469953/?lipi=urn%3Ali%3Apage%3Ad_flagship3_company_admin%3BUXLAZXmBRdGB89QgeEFQdA%3D%3D

What to Expect:

  1. Insider Insights: Gain a deeper understanding of cyclodextrins and their versatile applications across various industries, from pharmaceuticals to food and beyond.
  2. Expert Panel: Engage with a panel of distinguished experts who will share their knowledge, experiences, and perspectives on the latest developments in cyclodextrin research.
  3. Interactive Q&A: Pose your burning questions directly to the experts during the live session. Get real-time answers and insights that matter to you.
  4. Networking Opportunities: Connect with like-minded professionals, researchers, and industry leaders who share a passion for cyclodextrin science.

How to Participate:

  • Follow our LinkedIn page to receive notifications and updates about the live event.
  • Set a reminder for the scheduled date and time to ensure you don’t miss out on this unique opportunity.
  • Prepare your questions in advance to make the most of the interactive Q&A session.

Who Should Attend:

  • Researchers and scientists in the fields of chemistry, pharmaceuticals, and materials science.
  • Professionals in industries utilizing cyclodextrins, including pharmaceuticals, food and beverages, cosmetics, and more.
  • Students and academics interested in gaining insights into the latest advancements in cyclodextrin research.

Don’t miss this chance to be part of a vibrant community discussing the groundbreaking advancements in cyclodextrin science! Mark your calendars and join us for an engaging and informative live Q&A session.

Stay tuned for more updates and surprises during the event! 🚀

If you follow us, you know that we are keen to spread the word about cyclodextrins and create educational content. Now, we would like to get closer to you and answer any questions you may have directly. Formulation, analysis, chemistry, business, future applications, everything is on the table.

Feel free to join and ask directly from our CEO, Tamas Sohajda.

You can register and learn more here: 

📍 Location: LinkedIn Live – https://www.linkedin.com/events/7150478953097469953/?lipi=urn%3Ali%3Apage%3Ad_flagship3_company_admin%3BUXLAZXmBRdGB89QgeEFQdA%3D%3D

Folate-Appended Hydroxypropyl-β-Cyclodextrin Induces Autophagic Cell Death in Acute Myeloid Leukemia Cells

More and more uses of cyclodextrin as anticancer therapy agents come to light these days. The most recent is the research of Kumamoto University (who else) showing how Folate-Appended Hydroxypropyl-β-Cyclodextrin (FA-HP-β-CyD) Induces Autophagic Cell Death in Acute Myeloid Leukemia (AML) Cells.

As reported the cytotoxic activity of FA-HP-β-CyD against AML cells was stronger than that of HP-β-CyD. Also, FA-HP-CyD induced the formation of autophagosomes in AML cell lines. FA-HP-β-CyD increased the inhibitory effects of cytarabine and a BCL-2-selective inhibitor, Venetoclax, which are commonly used treat elderly AML patients. Notably, FA-HP-β-CyD suppressed the proliferation of AML cells in BALB/c nude recombinase-activating gene-2 (Rag-2)/Janus kinase 3 (Jak3) double-deficient mice with AML. These results suggest that FA-HP-β-CyD acts as a potent anticancer agent for AML chemotherapy by regulating.

IJMS | Free Full-Text | Folate-Appended Hydroxypropyl-β-Cyclodextrin Induces Autophagic Cell Death in Acute Myeloid Leukemia Cells (mdpi.com)

Figure 2
FA-HP-β-CyD induces apoptosis in HL-60, THP1, SKM1, and Kasumi1 cells. (A) HL-60, THP1, SKM1, and Kasumi1 cells were treated with 0 (medium only), 0.5, 1.0, and 1.5 mM of FA-HP-β-CyD for 72 h. After 72 h, cells were stained with Annexin V and PI. Representative FCM plots are shown (n = 3). (BE) Percentage of Annexin V-positive PI-negative cells after exposure to FA-HP-β-CyD for 72 h. (B) HL-60, (C) THP1, (D) Kasumi1, (E) SKM1 cells. Data represent the mean ± SEM of three independent experiments. * p < 0.05.

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

Apparently, cyclodextrin-based oligonucleotide delivery is becoming a hot research topic. This recent study from University of Nova Gorica – Tina Škorjanc, PhDDamjan MakucNora 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

Carbon quantum dots-containing poly(β-cyclodextrin) for simultaneous removal and detection of metal ions from water

Moungi Bawendi, Louis Brus and Aleksey Yekimov were awarded the Nobel Prize in Chemistry 2023 for the discovery and development of quantum dots. These tiny particles have unique properties and now spread their light from television screens and LED lamps.
Did you know the QDs can also be combined with cyclodextrin? In this application, they are used for water purification, particularly to remove metal ions from water.
Great work by André FajardoArtur Valente & colleagues

Carbon quantum dots-containing poly(β-cyclodextrin) for simultaneous removal and detection of metal ions from water – ScienceDirect

Preparation and evaluation of β-cyclodextrin-based nanosponges loaded with Budesonide for pulmonary delivery

Creating effective drug delivery systems for pulmonary applications is fascinating challenge. Recently, we have reported on the progress Aquilon Pharma made using cyclodextrins to deliver different APIs, their lead compounds being budasonide.
In this paper Francesco Trotta‘s and Aliasgar Shahiwala‘s groups proposes an alternative solution using cyclodextrin nanosponges. In vitro and in vivo studies showed almost complete drug release and drug absorption from the lungs in the initial 2 h for pure BUD, which were sustained up to 12 h from BUD loaded into nanosponges.

Preparation and evaluation of βcyclodextrin-based nanosponges loaded with Budesonide for pulmonary delivery – ScienceDirect

Finally, a novel cyclodextrin derivative in human clinics again!

Breaking news!
Alveron Pharma announced that it has completed a Phase 1 clinical study for OKL-1111, a new drug for the rapid treatment of Intracranial Haemorrhage (ICH) and other life-threatening bleeds associated with the use of anticoagulants or platelet inhibitors. OKL-1111 was well-tolerated in the trial with healthy human volunteers and showed no more adverse events above those in the placebo groups. Volunteers also received an anticoagulant and a pharmacodynamic effect was observed with OKL-1111 administration. In the prior non-clinical program, the drug reduced bleeding in a clinically relevant intracranial haemorrhage model using high doses of an anticoagulant. Furthermore, a broad-spectrum mode of action was demonstrated against all classes of anticoagulant and one platelet inhibitor to date in a standard haemostasis model.
Congratulations! Way to go!

Alveron Pharma completes successful first-in-human trial of OKL-1111

Cyclodextrin in Vaccines: Enhancing Efficacy and Stability

Great review from Gamze Varan at Hacettepe University on Cyclodextrin in Vaccines.
In the context of vaccines, cyclodextrins can effectively encapsulate antigens, ensuring their protection from degradation and improving their immunogenicity. Cyclodextrins offer stability advantages to vaccines by preventing the degradation of labile vaccine components during storage and transportation. Furthermore, cyclodextrins can serve as adjuvants, potentiating the immune response triggered by vaccines.

Future Pharmacology | Free Full-Text | Cyclodextrin in Vaccines: Enhancing Efficacy and Stability (mdpi.com)

Development of Liposome Systems for Enhancing the PK Properties of Bivalent PROTACs

Proteolysis-Targeting Chimeras (PROTACs) are a promising new technology in drug development. They have rapidly evolved in recent years, with several of them in clinical trials. While most of these advances have been associated with monovalent protein degraders, bivalent PROTACs have also entered clinical trials, although progression to market has been limited. One of the reasons is the complex physicochemical properties of the heterobifunctional PROTACs. A promising strategy to improve pharmacokinetics of highly lipophilic compounds, such as PROTACs, is encapsulation in liposome systems. Here liposome systems for intravenous administration to enhance the PK properties of two bivalent PROTAC molecules are described, by reducing clearance and increasing systemic coverage. A PROTAC-in-cyclodextrin liposome system was developed where the drug was retained in the liposome core. In PK studies at 1 mg/kg for GNE-01 the PROTAC-in-cyclodextrin liposome, compared to the solution formulation, showed a 80- and a 380-fold enhancement in AUC for mouse and rat studies, respectively. We further investigated the same PROTAC-in-cyclodextrin liposome system with the second PROTAC (GNE-02), where we monitored both lipid and drug concentrations in vivo. Similarly, in a mouse PK study of GEN-02, the PROTAC-in-cyclodextrin liposome system exhibited enhancement in plasma concentration of a 23× increase over the conventional solution formulation. Importantly, the lipid CL correlated with the drug CL. Additionally, we investigated a conventional liposome approach for GNE-02, where the PROTAC resides in the lipid bilayer. Here, a 5× increase in AUC was observed, compared to the conventional solution formulation, and the drug CL was faster than the lipid CL. These results indicate that the different liposome systems can be tailored to translate across multiple PROTAC systems to modulate and improve plasma concentrations. Optimization of the liposomes could further improve tumor concentration and improve the overall therapeutic index (TI). This delivery technology may be well suited to bring novel protein targeted PROTACs into clinics.
This is a unique industrial collaboration between GenentechArvinas & Bristol Myers Squibb.
#cyclodextrin #liposome #drugdelivery

Pharmaceutics | Free Full-Text | Development of Liposome Systems for Enhancing the PK Properties of Bivalent PROTACs (mdpi.com)