Using CDs to stabilize drugs chemically is rather frequently used. But did you know that they can also be used to stabilize radiopharmaceuticals? According to the patent of GE HealthCare (Kristine Opsvik Wikene; Kahn Imtiaz Ahmed; Graeme McRobbie) combined with a radiostabilizer (like ascorbic acid), a cyclodextrin as co-stabilizer improves the stability of radiopharmaceuticals compared to using a conventional stabilizer.
See the full patent on Espacenet.
We are proud to share Milo Malanga‘s most recent collaboration paper with Hacettepe University on creating nanoplexes via cationic cyclodextrin polymer, 5-Fluorouracil, and Interleukin-2 based on the opposite charge interaction of macromolecules without undergoing any structural changes or losing the biological activity of Interleukin-2. In the colorectal tumor-bearing animal model, survival rate, antitumor activity, metastasis, and immune response parameters were assessed using a cyclodextrin derivative, which was found to be safe based on the ALT/AST levels in healthy mice.
Histomorphometric analysis showed that the groups treated with the nanoplex formulation had significantly fewer initial tumors and lung foci when compared with the control. The dual drug-loaded nanoplex could be a promising drug delivery technique in the immunochemotherapy of colorectal cancer.
Safiye Akkın, Gamze Varan, Anıl Işık, Petek Korkusuz, Erem Bilensoy et al.
Have you ever wondered how cyclodextrins fit into modern, fancy formulation technologies like 3D printing? Nunzio Denora and his group at Università degli Studi di Bari and Institute of Crystallography – CNR show how to make budesonide-loaded mini-tablets using direct cyclodextrin-based powder extrusion 3D printing.
Monica Pistone, Giuseppe Francesco Racaniello, rosanna rizzi, Rosa Maria Iacobazzi, Ilaria Arduino, Antonio Lopalco, Angela Assunta Lopedota
University of Science and Technology Beijing presents a very unique use of CDs:
Anti-agglomerate agents (AAs) are a cost-effective method to prevent hydrates from clogging submarine oil/gas pipelines. However, conventional AAs such as Span 80 is not applicable in oil/gas pipelines rich in asphalt because asphalt is easy to occupy the binding sites on the water droplet surface. On the other hand, CDs show excellent anti-agglomerate characteristics in oil–water systems containing asphalt by forming stable hydrogen bonds with water molecules. Compared with Span 80, the initial contact time between water droplets and hydrate is delayed by five times after adding CD molecules. CD-asphalt interaction prevents water droplets from spreading on the hydrate surface by maintaining the stability of the emulsion.
The unique properties of CD provide a molecular basis for developing more green and efficient AAs.
Last week we shared applications of cyclodextrin in various types of cancer, and a discussion was triggered byTamas Sohajda about “why is it always HPBCD that is studied.” In this paper from Kumamoto University, JAPAN, by Keiichi Motoyama, Mannose-methyl-β-cyclodextrin is applied to suppress tumor growth by targeting colon cancer cells and tumor-associated macrophages.
See the full article here.
After sharing news on treating lymphedema, we came across another potential therapeutic use of cyclodextrin. In this preprint from Hefei University of Technology and Emory University authors demonstrate that 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) inhibited the growth and metastasis of triple-negative breast cancer (TNBC) both in vitro and in vivo, although the underlying mechanisms are unclear.
Cholesterol supplementation can attenuate HP-b-CD-inhibited TNBC growth and metastasis both in vitro and in vivo. In vivo, HP-β-CD promoted the infiltration of T cells into the tumor microenvironment (TME) and improved the exhaustion of CD8+ T cells via reducing endoplasmic reticulum (ER) stress and immune checkpoint molecules. Additionally, HP-β-CD inhibited the recruitment of tumor-associated macrophages to the TME by reducing the CCL2-p38MAPK-NF-kB axis. HP-β-CD also inhibited the epithelial-mesenchymal transition (EMT) of TNBC cells mediated by transforming the growth factor-b (TGF-b) signaling pathway.
In summary, the data in the current study suggest that HP-β-CD effectively inhibited the proliferation and metastasis of TNBC and melanoma, highlighting HP-β-CD may be a potential general antitumor clinical drug.
An interesting application is highlighted in the patent of RemeGen荣昌生物: methyl-BCD is used in antibody-drug conjugate formulations where the primary benefit is that ADC dose can be lowered (due to higher efficacy), which leads to mitigating safety concerns lowering costs, and patient treatment costs. Fascinating, huh? (Figure: Araris Biotech AG)
See the full patent on Espacenet.
A fascinating patent application by Hologic, Inc. using CDs in enzyme formulations for nucleic acid amplification. The compositions are also useful in mitigating the inhibitory effect of sample extraction detergents.
See the full patent on PatentScope
This is a real delicacy for #carbohydrates and #cyclodextrin lovers from the group of Graziella Vecchio – Università di Catania (Luana La Piana, Livia Basile, Chiara Ragusa et al.). They synthesize and characterize two new β and γ-cyclodextrin dimers and compare their complexation behavior. The two cavities in the same molecule significantly improve the stability of inclusion complexes – particularly investigated cholic acid, cholesterol, and doxorubicin as guests.
While the mainstream use of CDs in pharma is solubilization, improving chemical stability is close to 2nd most popular, even though it is more complicated to achieve. This patent by Thorsteinn Loftsson (Oculis S.A.) and Zoltán Fülöp encorporates a nice case study of preventing the oxidation of corticosteroids.
See the full patent on PatentScope