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

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.

Passive, active and endogenous organ-targeted lipid and polymer nanoparticles for delivery of genetic drugs

drug delivery, ,

As fellow stakeholders in developing novel drug delivery in gene therapy, we greatly admire the review of Sean Dilliard and Daniel Siegwart from The University of Texas Southwestern Medical School describing passive, active and endogenous organ-targeted lipid and polymer nanoparticles. Amazing compilation!

See the full article here

Use cyclodextrins as a radiostabilizer

drug delivery, Today's cyclodextrin, , ,

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.



Synergistic Antitumor Potency of a Self-Assembling Cyclodextrin Nanoplex for the Co-Delivery of 5-Fluorouracil and Interleukin-2 in the Treatment of Colorectal Cancer

drug delivery, , ,

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.

See the full article here

β and γ-Cyclodextrin dimers: design, characterization and in silico studies to explore the cooperative effect of the cavities

carbohydrates, drug delivery

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.

See the full article here.

Hexapeptide decorated β-cyclodextrin delivery system for targeted therapy of bone infection

carbohydrates, drug delivery

Fascinating cyclodextrin conjugation chemistry from Southwest Jiaotong University in order to target the hydroxyapatite component of the bone. We are also highly involved in conjugating peptides and carbohydrates to create actives and drug delivery systems. Have you ever considered a peptide-CD conjugate for such an application?

See the full article here

Sulfobutylether-β-cyclodextrin: A functional biopolymer for drug delivery applications

drug delivery, Today's cyclodextrin

If you even used CDs, you probably are familiar with SBECD. In this review, there is a nice colleaction of this parenteral excipient’s current and potential future applications.

Rucha Kothawade, Ashwini Markad, Sagar Pardeshi, Prashant Chaudhari, Marcela Longhi, Namdev Dhas, Jitendra Naik, Mónica Cristina García, Dr. Chandrakantsing Pardeshi [Ph.D.]

See the full article here

Co-Delivery of 8-Hydroxyquinoline Glycoconjugates and Doxorubicin by Supramolecular Hydrogel Based on α-Cyclodextrin and pH-Responsive Micelles for Enhanced Tumor Treatment

drug delivery, ,

Two birds with one stone:
This study of the Silesian University of Technology and the Polish Academy of Sciences is close to our hearts as we both deal with glycoconjugates and cyclodextrin. They show the delivery of 8-Hydroxyquinoline Glycoconjugates and Doxorubicin using ACD-based hydrogel for enhanced tumor treatment.

Monika D. Gabriela Pastuch Piotr Kurcok 

See the full article here

Weekly round-up of other carbohydrate-related articles (2022/47)

carbohydrates, drug delivery, drug development, drug discovery

I.
Great review from Universidade de Coimbra (Ana Cláudia Paiva-Santos, Laura Ferreira, Filipa Mascarenhas Melo, Sofia Rabaça, Francisco Veiga), Mewar University (Dr. Ankita Mathur), Sharda University, University at Buffalo (Dr. Prabhanjan Giram), Shivaji University, University of Zabol (Abbas Rahdar), Shanghai Jiao Tong University (Faisal Raza 费赛), Faculdade de Ciências Farmacêuticas – Unicamp (ENG: Pharmacy School – University of Campinas) (Priscila Mazzola) on dermatology and cosmetic applications

Read the full article here

II.
Beta-Cyclodextrins as affordable antivirals to treat coronavirus infection

Read the full article here

III.
Honestly, I am not sure how mankind will handle medication related to space travel. That will be a huge challenge that needs to be studied asap. Recently, the interaction behavior of remdesivir with CDs was studied at ISS (pp 53)

See the NASA e-book here

IV.
How cool is it that you can use CDs to stabilize antigens? Super cool 🙂
Polypseudorotaxane hydrogels based on cyclodextrin and polyethylene glycol significantly improved the stability of antibody preparations and showed no serious adverse effects after subcutaneous injection, suggesting the possibility as safe vaccine formulations to stabilize an antigen protein.
Daiichi University of Pharmacy
Kumamoto University, JAPAN
Hiroshi Itou Hidetoshi Arima Keiichi Motoyama

Read the full article here

V.
Enrichment of bread with α-CD resulted in positive effects on postprandial glycaemia and induced satiety. The incorporation of encapsulated hydroxytyrosol offered similar overall acceptability due to the bitter taste-masking effect provided by α-CD and a slightly additional positive effect in postprandial glycaemia and satiety. The development of foods with favorable metabolic effects is of great importance for the prevention of chronic diseases. The study was prospectively registered in clinicaltrials.gov (NCT04725955, date: 27th January 2021).
Harokopio University of Athens – Panagiota Binou, Athena Stergiou, Nikolaos Tentolouris, Vaios K.

See the full article here

VI.
Is the humid autumn whether messing up your hair? Keep calm and use CD-formulations (L’Oréal invention – Cho-Cho Khine and Ronak Rughani) for providing lasting curl definition and/or frizz and/or volume control to hair, even in high humidity.

See the full patent here