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

Voriconazole Eye Drops: Enhanced Solubility and Stability through Ternary Voriconazole/Sulfobutyl Ether β-Cyclodextrin/Polyvinyl Alcohol Complexes

drug delivery, Today's cyclodextrin, ,

This is a wonderful example of how something known (voriconazole-CD formulation) could be turned into something innovative. Researchers from Chulalongkorn University and Iceland University developed voriconazole eyedrops which shows high mucoadhesion, sustained release, good ex vivo permeability through the porcine cornea, and no sign of irritation. The stability study revealed that VCZ eye drops provide a shelf-life of more than 2.5 years at room temperature, while a shelf-life of only 3.5 months was observed for the extemporaneous Vfend® eye drops.

Hay Man Saung Hnin Soe, Khanittha Kerdpol, Thorsteinn Loftsson Phatsawee Jansook et al

Targeting bacterial virulence as a novel treatment against AMR infections

drug development, ,

Have you known that Arivin Therapeutics uses cyclodextrin for targeting bacterial virulence as a novel treatment against AMR infections? Among their MoA claims, the following are listed:
– Targeting virulence factors is effective, also against extensively resistant isolates
– Targeting virulence avoids rapid resistance
– Direct reduction in inflammatory responses
– Potentiates the function of antibiotics
Also, there is a spectacular video about how CDs develop their effect as antibacterials.

https://arivintx.com/our-science

Incorporation of Hydrophilic Macrocycles Into Drug-Linker Reagents Produces Antibody-Drug Conjugates With Enhanced in vivo Performance

Today's cyclodextrin, ,

Antibody-drug conjugates (ADCs) have begun to fulfill their promise as targeted cancer therapeutics with ten clinical approvals to date. Recently the role that linker-payload reagent design has on the properties of ADCs has been highlighted as an important consideration for developers. In this paper from Abzena, the effect of incorporating hydrophilic macrocycles like cyclodextrin into reagent structures on the in vitro and in vivo behavior of ADCs.

Nick Evans, Ruslan Grygorash, Nicolas Camper, Mark Frigerio, Matthew Bird et al

See the full article here

Disease management to disease modification – removing plaque to undo atherosclerosis

Today's cyclodextrin, ,

You can read a great interview with folks from Cyclarity Therapeutics at Longevity.Technology. Since they are one of the few companies developing tailor-made CDs to tackle a major disease, this is certainly worth attention.
“Cyclarity’s approach to true disease medication, and therefore reversal of age-related disease, without doubt, offers a great deal of promise for investors, for healthcare systems in the US and globally, and most of all for those affected by the atherosclerosis-related disease.
. . . this may be the perfect opportunity for Cyclarity to enter the field, as it is one of the few solutions available that addresses the limiting factors of previous therapies both from a scientific perspective and from a market perspective.”

See the full article here

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


Using heparan sulfate octadecasaccharide (18-mer) as a multi-target agent to protect against sepsis

drug discovery,

Fascinating research from University of North Carolina at Chapel Hill, The State University of New York and Rensselaer Polytechnic Institute on using heparan sulfate octadecasaccharide (18-mer) as a multi-target agent to protect against sepsis.

Yongmei Xu, Katelyn Arnold, Fuming Zhang, Vijayakanth Pagadala, Robert Linhardt et al.

See the full article here.

A composition for activating plant’s natural defense mechanisms to extend the shelf life and methods thereof

Today's cyclodextrin, ,

The agricultural use of CDs is often neglected, so here is an excellent example of exploiting their potential in this field. This includes the application of the encapsulated powder of the active ingredient, which is released in a sustained manner near the farm/agricultural produce. When the volatile active ingredient is released, it slows down the ethylene biosynthesis pathway and restricts microbial growth of fresh produce without any expensive technologies (refrigeration) and harmful chemicals (toxic). It can be adopted to any stage of the fruits and vegetable supply chain.

See the full patent on Patentscope

First-in-Class Small Molecule Drug Approvals of 2022

drug delivery, drug discovery,

First-in-Class Small Molecule Drug Approvals of 2022
Great collection by Drug Hunter.

Of the 36 novel small-molecule and large-molecule drugs approved by the FDA in 2022, 18 were first-in-class approvals, including 9 small molecules (excluding atoms).

Some of the notable small molecule first-in-class approvals of 2022 include:
Sunlenca (lenacapavir): the first approved drug targeting HIV-1 capsid, indicated for multi-drug resistant HIV with an impressive bi-annual dosing regimen (Gilead Sciences)

Sotyktu (deucravacitinib): the first approved de novo deuterated drug – an oral, allosteric tyrosine kinase 2 (TYK2) inhibitor for moderate-to-severe plaque psoriasis (Bristol Myers Squibb)

Ztalmy (ganaxolone): the first neurosteroid to be studied for epilepsy, approved for treating seizures in cyclin-dependent kinase-like 5 deficiency disorder, an oral GABA-A receptor modulator (Marinus Pharma) – a cyclodextrin-enabled formulation

Pyrukynd (mitapivat): the first approved therapeutic for pyruvate kinase (PK) deficiency – an oral pyruvate kinase activator that improves hemolytic anemia (Agios Pharmaceuticals)

Voquezna (vonoprazan): the first potassium-competitive acid blocker that acts via reversible potassium-competitive ion binding, approved for Helicobacter pylori infection (Phathom Pharmaceuticals)

See the full article here.