Structure-activity relationship of modified amphiphilic cationic cyclodextrins for enhanced siRNA delivery

Egyéb kategória, Today's cyclodextrin, ,

Today’s cyclodextrin was a little gift under CarboHyde’s and GENEGUT’s Christmas tree.

This study identified the structural modifications that enhance gene delivery activity of a range of cationic amphiphilic CDs, including both β- and γ-CD.

Each CDs incorporated a C12 lipid chain on the primary face of the CD. On the secondary rim, at positions C2 and C3, either primary or tertiary amine groups.

A comparative in vitro study was conducted to assess the gene silencing efficacy of these nanoparticles using the luciferase reporter gene in A549-luc cells.

Gene silencing levels for both β- and γ-CDs increased when modified with a primary amine compared to a tertiary amine group at position C2. Gene expression inhibition was further improved when the CDs were functionalized with amine functionalities at positions C2 and C3.

Modification of the secondary side of γ-cyclodextrins with two sets of primary amine functionalities via a thiopropyl linker, as compared to a triazole linker, achieved up to 80% gene knockdown, regardless of dose.

Ayse Kont, Monique Mendonça, PhD, Milo Malanga PhD, Kristóf Felegyi, Andrew Lindsay, Michael Cronin, Mary Cahill, Caitriona O’Driscoll

Structure-activity relationship of modified amphiphilic cationic cyclodextrins for enhanced siRNA delivery – ScienceDirect

cyclodextrin, cationic, carbohyde

FORMULATION DEVELOPMENT – Solubility-Enhancing Technologies in Pharmaceutical Development, a Mini-Review

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Great article in this month’s issue of Drug Development & Delivery featuring cyclodextrins and other solubilization techniques.

Ardena‘s Drug Product team, led by Vincent Levet (Director, Formulation Development and Production) and Timothy Pas (Group Leader, Formulation Development and Production), has just published this technical article that explores innovative formulation strategies aimed at addressing solubility and bioavailability challenges in poorly soluble drugs. The article focuses on advanced techniques like Amorphous Solid Dispersions (ASDs), lipid-based formulations, Nanosuspensions, and hashtag#Cyclodextrin complexes.

The team highlights how these approaches can accelerate time-to-market while ensuring optimal therapeutic outcomes.

FORMULATION DEVELOPMENT – Solubility-Enhancing Technologies in Pharmaceutical Development, a Mini-Review (drug-dev.com)

A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses

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Scientists create first mouse model with complete, functional human immunesystem and a human-like gutmicrobiome that is capable of mounting specific antibody responses.

Such a model would have unlimited uses in pharma development. The work of Paolo Casali et al groundbreaking and will disrupt the animal models we use for efficacy and safety studies. How would you use this model first? I imagine studies with vaccines probably…

Nature Immunology, 5 July 2024

A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses | Nature Immunology

Carbohyde blog

Anti–inflammatory effects of cyclodextrin nanoparticles enable macrophage repolarization and combat inflammation

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Today’s cyclodextrin is about the intrinsic anti-inflammatory properties of CDs.

Inflammation is an essential contributor to the pathophysiology of numerous diseases, and dysregulation of the involved signaling cascades often culminates in uncontrollable disease progression and, ultimately, chronification. Effectively addressing these disorders is challenging due to their inherent complexity and the need to mitigate inflammation while preserving essential immune functions.

Amphihilic cyclodextrin-based nanoparticles exhibit significant downregulation of crucial pro-inflammatory markers, along with changes in inflammasome activation and the lipid profile of pro-inflammatory macrophages after CD nanoparticle application. The findings of this study underscore the potential of cyclodextrin-based nanoparticles as versatile biomaterials for treating the complex pathophysiology of various acute and chronic inflammation-associated disorders.


Anti–inflammatory effects of cyclodextrin nanoparticles enable macrophage repolarization and combat inflammation | Research Square
Felix E. B. Brettner, Annika Haessler, Jonas Schreiner et al from Goethe University Frankfurt

CarboHyde blog

Cyclodextrin derivatives for the treatment of gout and hyperuricemia

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Inspiring research and patent from our collaborators at Università degli Studi di Torino and Universidad de Murcia

Adrián Matencio Durán, Francesco Trotta, Yousef Khazaei Monfared, Fabrizio Caldera, and José Manuel López Nicolás disclosed an invention in which various cyclodextrins are investigated in the therapy of gout and hyperuricemia.

WO2024133757 CYCLODEXTRIN DERIVATIVES FOR THE TREATMENT OF GOUT AND HYPERURICEMIA (wipo.int)

Stepwise Nitric Oxide Release and Antibacterial Activity of a Nitric Oxide Photodonor Hosted within Cyclodextrin Branched Polymer Nanocarriers

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Fresh from the oven, is a paper from our long-term collaboration with Università di Catania and Salvo Sortino‘s team about Cyclodextrin Branched Polymer Nanocarriers.

Encapsulation of the NO photodonor within biocompatible neutral, cationic, and anionic β-cyclodextrin branched polymers as suitable carriers leads to supramolecular nanoassemblies, which exhibit the same nature of the photochemical processes but NO photorelease performances enhanced by about 1 order of magnitude when compared with the free guest.

Antibacterial tests carried out with methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii demonstrate an effective antibacterial activity exclusively under light activation and point out a differentiated role of the polymeric nanocarriers in determining the outcome of the antibacterial photodynamic action.

Stepwise Nitric Oxide Release and Antibacterial Activity of a Nitric Oxide Photodonor Hosted within Cyclodextrin Branched Polymer Nanocarriers | ACS Medicinal Chemistry Letters

Hopefully, our CSO Milo Malanga will continue to promote such flourishing collaborations.

Stepwise Nitric Oxide Release and Antibacterial Activity of a Nitric Oxide Photodonor Hosted within Cyclodextrin Branched Polymer Nanocarriers

Egyéb kategória

Fresh from the oven, a paper from our long-term collaboration with Università di Catania and Salvo Sortino‘s team about Cyclodextrin Branched Polymer Nanocarriers.

Encapsulation of the NO photodonor within biocompatible neutral, cationic, and anionic β-cyclodextrin branched polymers as suitable carriers leads to supramolecular nanoassemblies, which exhibit the same nature of the photochemical processes but NO photorelease performances enhanced by about 1 order of magnitude when compared with the free guest.

Antibacterial tests carried out with methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii demonstrate an effective antibacterial activity exclusively under light activation and point out a differentiated role of the polymeric nanocarriers in determining the outcome of the antibacterial photodynamic action.

Hopefully, our CSO Milo Malanga will continue to promote such flourishing collaborations.

Stepwise Nitric Oxide Release and Antibacterial Activity of a Nitric Oxide Photodonor Hosted within Cyclodextrin Branched Polymer Nanocarriers | ACS Medicinal Chemistry Letters

Giving you my heart becomes reality

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Insight Heart is a 3D interactive app that offers a comprehensive and immersive journey into the human heart. It features high-resolution visuals, real-time insights, and interactive elements, making medical education engaging, accessible and enjoyable for students, physicians, and patients anytime and anywhere.

Its key features include a spatial computing experience, multi-user sessions, filter system exploration, and condition visualizations, which allow for remote and efficient collaboration, in-depth understanding of the heart’s complex structures, and an immersive experience of heart conditions.

This provides a new level of understanding and immersion in medical education.

INSIGHT HEART on Apple Vision Pro (youtube.com)

Solving the puzzle of 2-hydroxypropyl β-cyclodextrin: Detailed assignment of the substituent distribution by NMR spectroscopy

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Its our pleasure to announce our most recent paper on

Solving the puzzle of 2-hydroxypropyl β-cyclodextrin: Detailed assignment of the substituent distribution by NMR spectroscopy

resulting from a collaboration with Semmelweis University and Aalborg University.

Recognizing that the distribution of substituents significantly influences the complexation ability and overall activity of the derivative, primarily by altering cavity dimensions, we present a straightforward and non-destructive method based on liquid state NMR spectroscopy to analyze the positions of the hydroxypropyl sidechains. This method relies on a single set of routine experiments to establish quantitative assignment and it provides a simple yet effective tool to disclose the substitution pattern of this complex material, utilizing easily accessible (400 MHz NMR) instrumentation.

Szabolcs Béni, Eszter Kalydi, Thorbjørn Terndrup Nielsen, Reinhard Wimmer, Milo Malanga PhD

Solving the puzzle of 2-hydroxypropyl β-cyclodextrin: Detailed assignment of the substituent distribution by NMR spectroscopy – ScienceDirect