Adamgammadex vs Sugammadex

Check out this fascinatnig discussion on next future of cyclodextrin-based antidotes and scavengers by J Robert Sneyd adn Jennifer Hunter.

Spoiler alert: Phase 3 clinical trials suggest that Adamgammadex is slightly less potent than sugammadex and has a non-inferior speed of onset. In a multicentre trial of 310 patients, there was a suggestion of a lower incidence of allergic responses and recurarisation after adamgammadex compared with sugammadex.

If you are also thinking about creating a special cyclodextrin like that, this may be useful for you: Custom synthesis of cyclodextrins – www.carbohydesolutions.com

Is adamgammadex the brother of sugammadex or the next generation of reversal agent? – British Journal of Anaesthesia (bjanaesthesia.org)

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

We have known for a while that methylated β-cyclodextrin (MβCD) can extract cholesterol from lipid rafts and induce apoptosis in cancer cells by inhibiting activation of the PI3K-Akt-Bad pathway.

In this study from Kumamoto University (Keiichi Motoyama), MβCD with mannose (Man-MβCD) is assessed for targeting colon cancer cells expressing the mannose receptor (MR) and tumor-associated macrophages (TAM). Man-MβCD showed a significantly greater level of cellular association with colon-26 cells and M2 macrophages, and much more prominent anticancer activity than that of MβCD against MR-positive colon-26 cells. These results revealed that autophagy was the main mechanism of cell death associated with Man-MβCD. Furthermore, compared with MβCD, Man-MβCD significantly reduced tumor development following intravenous delivery to tumor-bearing mice, with no apparent side effects. Thus, Man-MβCD has the potential to be a novel anticancer drug.

If you would like to try something like this, check out this site for ideas: Custom synthesis of cyclodextrins – www.carbohydesolutions.com

Therapeutic polypseudorotaxane hydrogels

Qrons Inc. – ido merfeld propose using polyrotaxanes (which are “necklace” like molecules where the “pearls” are cyclodextrins and in this invention the “chain” is a polymer of ethylene oxide) for manufacturing a medicament for Central Nervous System. The proposed examples include piping into the brain for treatment of traumatic brain injury.
If you are interested in creating such innovative constructs from cyclodextrins, check out this site for possibilities, we can probably help: Custom synthesis of cyclodextrins – www.carbohydesolutions.com

WO2023194821 THERAPEUTIC POLYPSEUDOROTAXANE HYDROGELS (wipo.int)

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.

What are GLP-1s?


GLP-1-based therapies, such as GLP-1 receptor agonists, glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors, improve glucose control through various mechanisms including increased insulin secretion, slower gastric emptying, and reduced postprandial glucagon and food intake. These therapies do not typically cause hypoglycemia on their own but may occur when used in combination with additional glycemic drugs. Apart from GLP-1 therapies reducing glucose levels (HbA1c) they also offer additional benefits which will influence the prescriber in finding the correct drug for a specific patient outcome. Dulaglutide, liraglutide and subcutaneous semaglutide have been approved for reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus with established cardiovascular disease, dulaglutide is approved for use in type 2 diabetes mellitus with multiple risk factors, and both liraglutide and semaglutide have been approved for chronic weight management.

Drug shortages of long-acting GLP-1 receptor agonists and dual GLP-1/GIP receptor agonist have emerged unexpectedly and persisted through the first quarter of 2023. This occurred due to an unexpected increase in demand without adequate adjustment in production. The shortage has created new access barriers for patients previously using or wishing to initiate these products for glycemic management, weight loss, and/or cardiovascular risk reduction.

FDA-Approved Alzheimer’s Medications

⚫ 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

In Vitro Biological Properties of Cyclodextrin-Based Polymers: Interaction with Human Serum Albumin, Red Blood Cells and Bacteria

Cyclodextrin polymers have increasing importance, as they are evaluated more and more frequenty in drug delivery solutions and non-pharma applications. This important paper deals with critical aspects of their behavior, such as interaction with human serum albumin, red blood cells bacteria.

Cyclodextrin derivatives and their polymers did not affect the secondary structure content of human serum albumin, which might mean a mild effect on the structural and functional properties of the main blood plasma protein.

Using the hemolysis test, it was found that polymers interact with red blood cells and can be assigned to non-hemolytic and slightly hemolytic groups as biocompatible materials, which are safe for in vivo use.

The cyclodextrins and their polymers did not extract proteins from bacterial cell walls and did not demonstrate any antibacterial activity against Gram-positive and Gram-negative strains.

Polysaccharides | Free Full-Text | In Vitro Biological Properties of Cyclodextrin-Based Polymers: Interaction with Human Serum Albumin, Red Blood Cells and Bacteria (mdpi.com)

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