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

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

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

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

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

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 DeviCristina CasadidioMaria Rosa GigliobiancoPiera 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?

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

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)

Synthesis and Preliminary Evaluation of an ASGPr-Targeted Polycationic β-Cyclodextrin Carrier for Nucleosides and Nucleotides

As our interest to use cyclodextrin in genetherapy as superior drugdelivery tools continue, we welcome papers like this, where cationic CD polymers are used for nucleotide formulation.
Leonard Wiebe and coworkers from University of Alberta development a carrier designed to effect selective transmembrane internalization of nucleotides via the asialoglycoprotein receptor.

Pharmaceutics | Free Full-Text | Synthesis and Preliminary Evaluation of an ASGPr-Targeted Polycationic β-Cyclodextrin Carrier for Nucleosides and Nucleotides (mdpi.com)


New Captisol (Ligand Pharmaceuticals) enabled API on the market!

Today’s cyclodextrin:

Eisai Co., Ltd. obtained marketing authorization approval in January 2024 from the Japanese Ministry of Health, Labour and Welfare for the injection formulation of its in-house discovered antiepileptic drug (AED) Fycompa® (perampanel) in Japan as an alternative therapy when oral administration is temporarily not possible. Fycompa is formulated with Captisol®, a Ligand technology.

About perampanel (Fycompa®)
Perampanel is a first-in-class anti-epileptic agent (AED) discovered and developed by Eisai. With epileptic seizures being mediated by the neurotransmitter glutamate, the agent is a highly selective, noncompetitive AMPA receptor antagonist that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at AMPA receptors on postsynaptic membranes. Perampanel is currently approved in more than 75 countries and territories, including Japan, China, and other countries in Europe and Asia, as an adjunctive treatment for partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 12 years of age and older. In addition, perampanel has been approved in more than 70 countries, including Japan, Europe, and Asia, for treatment as an adjunctive therapy for primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older. In Japan and China, perampanel is approved for monotherapy and adjunctive use in the treatment of partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 4 years of age and older. In Europe, the approved age range is 4 years of age and older for the adjunctive treatment of partial-onset seizures (with or without secondarily generalized seizures) and 7 years of age and older for the treatment as an adjunctive therapy for primary generalized tonic-clonic seizure. A tablet, fine granule formulation, and injection formulation have been approved in Japan. An oral suspension formulation and tablet have been approved in Europe and China. In January 2023, the commercial rights in the United States were transferred to Catalyst Pharmaceuticals, Inc.