Reduction of thyroid radioactive iodine exposure by oral administration of cyclic oligosaccharides

drug development, ,

Radioactive iodine may cause thyroid cancer and hypofunction and accordingly must be properly managed. If the absorption of radioactive iodine is suppressed, it can be expected to lead to a reduction in thyroid exposure. This study the inhibition of radioactive iodine absorption by the oral administration of α-cyclodextrin is shown in a murine model. The uptake of radioactive iodine into the thyroid gland in mice administered with radioactive iodine and an α-cyclodextrin solution was approximately 40% lower after 24 h. The finding that oral uptake of α-cyclodextrin has an inhibitory effect on the transfer of radioactive iodine to the thyroid gland has potential for application in many fields such as food, pharmaceuticals, nuclear emergency preparedness, and medicine.
Kumamoto University, JAPAN

See the full article on nature.com

Lipid-based RNA formulations suitable for therapy

Today's cyclodextrin, , , ,

today’s cyclodextrin:
In this invention, BioNTech SE provides a method of producing a composition comprising RNA lipoplex particles. The main focus of the description is antitumoral therapy.
In the formulation itself, the aqueous colloidal suspension of liposomes is combined with an aqueous solution comprising RNA, thereby producing the composition comprising RNA lipoplex particles. The formulation requires frozen storage conditions; hence the use of cyroprotectant is necessary. The invention proposes mono- di- and oligosaccharides to protect such compositions, including various cyclodextrins and cyclodextrin polymers.
The use of cyclodextrins as cryoprotectants and stabilizers in biopharmaceutical formulations is an emerging technology.

Dr. Hossam Hefesha, Heinrich Haas, Ferdia Bates, Christian Hotz
Katalin Karikó

See the full patent Patentscope

A mannosylated polymer with endosomal release properties for peptide antigen delivery

drug delivery, ,

The University of Washington introduces Man-VIPER, a self-assembling, pH-sensitive, mannosylated polymeric peptide delivery platform that targets dendritic cells in the lymph nodes, encapsulates peptide antigens at physiological pH and facilitates the endosomal release of antigens at acidic endosomal pH through conjugated membranolytic peptide melittin. In vivo, the Man-VIPER polymer demonstrated an adjuvant effect and induced the proliferation of antigen-specific cytotoxic T cells and helper T cells compared to free peptides and Man-AP. The antigen delivery with Man-VIPER-NR generated significantly more antigen-specific cytotoxic T cells than Man-VIPER-R in vivo. and Man-VIPER-NR exerted superior efficacy in a B16F10-OVA tumor model. These results highlight Man-VIPER-NR as a safe and powerful peptide cancer vaccine platform for cancer immunotherapy.

Dinh Chuong (Ben) Nguyen, Tran Luu, Omeed Yazdani, Patrick Stayton and Suzie Pun

See the full article here: A mannosylated polymer with endosomal release properties for peptide antigen delivery

Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia

carbohydrates, drug development, ,

Positive Phase 1/2 clinical data published on uproleselan (GMI-1271), a novel E-selectin antagonist that disrupts cell survival pathways, enhance chemotherapy response, improves survival in mouse xenograft and syngeneic models, and decreases chemotherapy toxicity in vivo.
The addition of uproleselan to chemotherapy was well tolerated, with high remission rates, low induction mortality, and low rates of mucositis, providing a strong rationale for phase 3 randomized confirmatory studies.
Brian Jonas, Jane Jane Liesveld, Dale Bixby, Paula Marlton, John Magnani, Helen Thackray, Eric Feldman, Pamela Becker et al. – GlycoMimetics

See the full clinical trials report here.

Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia

Treatment of cancer

carbohydrates, , , ,

This patent on CRLX-101, an experimental approach using camptothecin (CPT) to cancer chemotherapy, reminded us of a wonderful idea from Mark Davis (Caltech). In CRLX101, CPT is linked covalently through a glycine link to the linear copolymer CDP, which in turn consists of alternating subunits of beta-cyclodextrin and polyethylene glycol (PEG). The CRLX101 nanoparticle is water-soluble. After intravenous injection, active CPT is slowly released as the linkage is hydrolyzed. The size of the nanoparticle (20-50 nm in diameter) facilitates its extravasation in the more leaky vessels of tumors via the enhanced permeability and retention effect. As a result, the anticancer drug is enhanced and retained in the tumor tissue.
The new patent from Ellipses Pharma proposes novel applications dominantly in rectal cancer.
Amato Giaccia, Hanna Sanoff, Joel Tepper

Hyaluronan-Cyclodextrin Conjugates as Doxorubicin Delivery Systems

carbohydrates,

We love both chemistry and carbohydrates. So when people publish about conjugating carbohydrates with carbohydrates and their pharma applications, our hearts are full of inspiration and passion.
Check out how researchers from Università di Catania and Ospedale Policlinico San Martino propose using Hyaluronan-Cyclodextrin Conjugates as drug delivery tools!
Noemi Bognanni, Luana La Piana, Simone Strano, rosaria gangemi, Maria Teresa Cambria, Graziella Vecchio et al

See the full article here


Mannose-methyl-β-cyclodextrin suppresses tumor growth by targeting both colon cancer cells and tumor-associated macrophages

drug discovery, ,

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.

Hydroxypropyl-β-cyclodextrin inhibits the development of triple-negative breast cancer by enhancing antitumor immunity

drug development, ,

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.

See the full article here

The authors found that HP-b-CD inhibits the proliferation and metastasis of TNBC by reducing cholesterol levels. HP-b-CD promotes T cell recruitment to the TME and improves CD8+ T cell exhaustion. Additionally, HP-b-CD inhibits TAMs accumulation.

Synthesis, binding affinity, and inhibitory capacity of cyclodextrin-based multivalent glycan ligands for human galectin-3

carbohydrates, drug discovery,

Bathing in carbs: Lai-Xi Wang and his group from the University of Maryland reported the synthesis of cyclodextrin-based multivalent glycan ligands for human galectin-3. The GalNAc (Tn antigen) containing heptavalent ligand showed the highest affinity for human Gal-3 among the synthetic ligands tested, with an EC50 of 1.4 μM in binding to human Gal-3.

Link to the article

carbohyde, galectin, cyclodextrin