Cationic Cyclodextrin-Based Carriers for Drug and Nucleic Acid Delivery

Today's cyclodextrin, drug delivery

Check out our latest cyclodextrin review fresh from the oven on cationic cyclodextrins for drug and nucleic acid delivery.

This contribution to science is a fruit of our collaboration with Eötvös Loránd University and Semmelweis University (Szabolcs Béni and Adila Nazli).

Special thanks to Milo Malanga PhD and Tamas Sohajda as well as Bicyclos HEurope for the funding.

Cationic Cyclodextrin-Based Carriers for Drug and Nucleic Acid Delivery

Cationic Cyclodextrin-Based Carriers for Drug and Nucleic Acid Delivery

Synergistic effect of cyclodextrins and electrolytes at high concentrations on protein aggregation inhibition

drug delivery, Today's cyclodextrin, ,

Today’s cyclodextrin is about preventing protein aggregation.

I have posted a lot about how CDs can interact with proteins, CarboHyde even shared an educative deck on this earlier: CDs_in_protein_formulations.pdf

The research below from Kobe University and synplogen adds a new feature to this knowledge via exploring the Synergistic effect of cyclodextrins and electrolytes at high concentrations on protein aggregation inhibition:
Synergistic effect of cyclodextrins and electrolytes at high concentrations on protein aggregation inhibition – Journal of Pharmaceutical Sciences

Research highlights:
•High cyclodextrin (CD) and electrolyte concentrations synergistically stabilize biopharmaceutical proteins.
•HP-β-CD and Arg-HCl significantly increase the onset temperature of protein aggregation of immunoglobulin G, insulin, and adeno-associated virus vectors.
•This synergistic effect was not observed when sucrose was used instead of HP-β-CD.
•HP-β-CD and Arg-HCl combination effectively inhibits the formation of soluble and insoluble IgG aggregates during long-term storage.

The application of cyclodextrins in drug solubilization and stabilization of nanoparticles for drug delivery and biomedical applications

carbohydrates, drug delivery, drug development

Not many things get better with years passing but some do.
Things like:
– whiskey,
– wine
– blue jeans
– friendships
and Thorsteinn Loftsson

This was my first thought when reading this paper, which I coauthored with Hay Man Saung Hnin Soe and Phatsawee Jansook on cyclodextrin-based nanoparticles.

This review emphasizes the role of cyclodextrins (CDs) in stabilizing colloidal nanoparticles (NPs) and improving drug solubility. The integration of CDs with NPs offers a synergistic strategy that enhances drug delivery and expands the scope of biomedical applications. Furthermore, the review thoroughly explores the potential of CDs to boost the stability and therapeutic effectiveness of colloidal NPs, positioning them as promising candidates for advanced drug delivery systems

The application of cyclodextrins in drug solubilization and stabilization of nanoparticles for drug delivery and biomedical applications – ScienceDirect

Lipid nanoparticles for nucleic acid delivery

drug delivery, Today's cyclodextrin, ,

Today’s cyclodextrin is this great patent from Roquette‘s team, Tao Peng, Lucas Goh, Jeff Chang Shih Chieh on a new class of Lipid nanoparticles (LNPs) that can be used for nucleic acid delivery, wherein LNPs comprise a nucleic acid and a nonionic or cationic cyclodextrin compound.

How do you see the future of CDs in gene therapy? Will we see solutions commercialized in the future? In GENEGUT we certainly work towards this goal!

WO2024125823 LIPID NANOPARTICLES FOR NUCLEIC ACID DELIVERY (wipo.int)

Improving the therapeutic window of anticancer agents by β-cyclodextrin encapsulation: Experimental and theoretical insights

drug delivery, Today's cyclodextrin, ,

Today’s cyclodextrin is about the stabilization effect of CDs on proteins, yet from a different angle.

I shared a lot earlier about the potential of CDs replacing surface active agents, yet how about combining them?

This study from Roquette led by Rajeev Gokhale and Vinod T. investigates the collaborative impact of combining polysorbates and HPβCD as excipients in protein formulations. The introduction of HPβCD in formulations showed it considerably reduced aggregation in two model proteins, bevacizumab and ipilimumab, following exposure to various stress conditions. The diffusion interaction parameter revealed a reduction in protein-protein interactions by HPβCD.

The study suggests that combining these excipients can improve mAb stability in formulations, offering an alternative for the biopharmaceutical industry.

Improving the therapeutic window of anticancer agents by β-cyclodextrin encapsulation: Experimental and theoretical insights – ScienceDirect

mAb, monoclonal antibodies, carbohyde

Isosorbide mononitrate spray and preparation method

drug delivery, Today's cyclodextrin, ,

Today’s cyclodextrin is an innovative formulation of isosorbide mononitrate. In this patent, a cyclodextrin complex is prepared, suitable to develop sprays, having the advantages of quick response, small irritation, and convenience in use.

Isosorbide mononitrate is a medication primarily used for the prevention of angina pectoris, which is chest pain caused by reduced blood flow to the heart. It works by relaxing and widening blood vessels, which allows more blood and oxygen to reach the heart, thereby reducing the heart’s workload and helping to prevent episodes of chest pain. It belongs to a class of drugs known as nitrates.

Isosorbide mononitrate is used in a long-acting form, which is not suitable for relieving an acute angina attack but is used regularly to decrease the frequency and severity of angina episodes. It may also be used in other conditions as determined by a doctor, based on its vascular effects.

It is typically available in tablet form for oral administration. This medication is taken by mouth and is formulated as either immediate-release or extended-release tablets, depending on the intended dosing schedule and therapeutic need. The drug acts by releasing nitric oxide, which helps to relax and widen blood vessels, but the drug itself is solid in its delivery form.

Espacenet – Isosorbide mononitrate spray and preparation method thereof

Multifunctionality of cyclodextrin-based polymeric nanoparticulate delivery systems for chemotherapeutics, combination therapy, and theranostics

drug delivery, ,

As cancer remains one of the most challenging diseases to treat, scientists have developed various medications and therapeutic approaches to combat it. To protect drugs from degradation or inactivation, efficient delivery systems are required during administration. In this context, cyclodextrin-based polymeric nanosystems have emerged as an effective treatment approach against cancer.

Cyclodextrins are natural oligosaccharides that can trap water-insoluble molecules inside their hydrophobic core, making them valuable in pharmaceutical research. When combined with polymeric nanoparticles, CD-based delivery systems provide versatile and tunable profiles, thanks to the submicron-sized PNPs. Recent studies have shown that CD-based delivery systems can successfully be applied in combination therapy and theranostics, providing multifunctional advantages against cancer.

The article by Lakshmi Sathi Devi, Cristina Casadidio, Maria Rosa Gigliobianco, Piera Di Martino and Roberta Censi from University of Camerino further discusses different binding approaches, release mechanisms of CD-drug complexation, and characterization studies. Promoting CD to a polymeric and nanoscale has demonstrated improved tumor targeting, reduced side effects, and prolonged drug release in preclinical studies and clinical trials. Notably, CD-based delivery systems, including CALAA-01, CRLX101, and CRLX301, have shown promising results in treating cancer.

Overall, cyclodextrin-based polymeric nanosystems hold great potential in tackling the abnormalities behind cancer by providing an efficient drug delivery system.

Multifunctionality of cyclodextrin-based polymeric nanoparticulate delivery systems for chemotherapeutics, combination therapy, and theranostics – ScienceDirect


Drugs in Cyclodextrin in Liposomes: How a Suitable Formulation of an Active Substance Can Improve Its Efficiency?

drug delivery, Today's cyclodextrin,

today’s cyclodextrin:
Drugs in Cyclodextrin in Liposomes: How a Suitable Formulation of an Active Substance Can Improve Its Efficiency?

Great paper from Prof Geraldine Gouhier, François Estour and colleagues from Université de Rouen on the design of new drug delivery systems.

Liposome formulations are pivotal in medicine for their ability to improve drug solubility, allowing for targeted delivery directly to disease sites, which minimizes side effects. They enable controlled and sustained release of medications, reducing dosage frequency. Their ability to encapsulate a variety of substances makes them versatile for different treatments, significantly reducing toxicity and enhancing the stability of drugs, especially sensitive biological compounds. This ensures a more effective and safer therapeutic approach.

Discover how the innovative “drug-in-cyclodextrin-in-liposomes” method is revolutionizing drug delivery! Enhancing drug stability & release, this latest review dives into how these nano-carriers improve the efficacy of various drugs. 🧬💊

Processes | Free Full-Text | Drugs in Cyclodextrin in Liposomes: How a Suitable Formulation of an Active Substance Can Improve Its Efficiency? (mdpi.com)


SOLUBILIZING & STABILIZING TECHNOLOGY – CAPTISOL® – Part Perseverance & Part Serendipity

drug delivery, Today's cyclodextrin

today’s cyclodextrin:
The article on Captisol®, a solubilizing and stabilizing technology of Ligand Pharmaceuticals, highlights its evolution from uncertain beginnings to becoming a pharmaceutical industry staple, thanks to the perseverance of scientists and strategic partnerships, notably with Pfizer. Initially developed from the need for better drug formulation tools, Captisol has been integral in creating viable drug products, especially for poorly soluble and unstable molecules. Its proven safety, alongside innovations in production and application, has led to its inclusion in multiple FDA-approved drugs, with ongoing expansion into various administration routes and global regulatory acceptance​​.
#formulationdevelopment #drugdelivery

SOLUBILIZING & STABILIZING TECHNOLOGY – CAPTISOL® – Part Perseverance & Part Serendipity (drug-dev.com)