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.

Comparative investigation of pulmonary vasodilating effects of inhaled Nitric Oxide (NO) gas therapy and inhalation of SIN-1, a new drug formulation containing an NO-donor metabolite

Today’s cyclodextrin is a nice collaborative formulation and in vivo (porcine) study between Semmelweis University and Cyclolab R&D Ltd.
In the project, the hemodynamic effect of inhalative SIN-1a (the unstable active metabolite of molsidomine, stabilized by cyclodextrine) was studied. The pulmonary vasodilator effect of SIN-1 was dose dependent, and in case of larger dose it was comparable to that of iNO. However, the vasodilatory effects of SIN-1 inhalation was not limited to the pulmonary circulation, a significant and dose-dependent systemic vasodilation could also be documented.
My only regret here is not all contributors met the authors’ list finally.

Comparative investigation of pulmonary vasodilating effects of inhaled Nitric Oxide (NO) gas therapy and inhalation of SIN-1, a new drug formulation containing an NO-donor metabolite | European Heart Journal | Oxford Academic (oup.com)

Development of α-Cyclodextrin-Based Orally Disintegrating Tablets for 4-Phenylbutyrate

Today’s cyclodextrin:
One of the greatest features of CDs is that with a proper application (especially when the local CD concentration is relatively high), they can not only improve the solubility but also the permeability of compounds. For example, in the case of a peroral application, let’s say an orally disintegrating tablet. Not to mention that their taste masking potential is also of use in this case. 3 birds with one stone!

In this paper, you can find a great example of such a smart application. If you are interested in developing similar formulations, check out the first steps here: Formulation development – www.carbohydesolutions.com

Pharmaceutics | Free Full-Text | Development of α-Cyclodextrin-Based Orally Disintegrating Tablets for 4-Phenylbutyrate (mdpi.com)

Development of abiraterone acetate tablets with enhanced oral bioavailability

Today’s cyclodextrin
Reading this paper from Yeungnam University by Jong Oh Kim et al reminded me about a core application of CD’s: improving oral bioavailability of compounds. While this feature does not work generally on all compounds, it certainly does on the ones, where the poor solubility is the main cause of the low oral bioavailability. On the other hand, this feature of CD’s often make developing generic drugs with this excipients impossible, while creating improved/added value reformulations of repurposed APIs remains a target use.

If you have projects like this on your table, you might find it useful to check this website: Development of abiraterone acetate tablets with enhanced oral bioavailability | Journal of Pharmaceutical Investigation (springer.com)

Cyclodextrin-loaded nanobubbles reduce cholesterol and atherosclerosis in vivo

While the uses of cyclodextrin as active ingredients is emerging both by the number of target diseases, companies developing them and types of CDs used, their efficient delivery remains a challenge.
The nanobubbles presented here could incorporate the CDs, accumulate in the atherosclerotic lesions, the release of CD and the reduce the total plaque area in the entire aorta and eventually reduce cholesterol level in mice plasma.
Cyclodextrin-loaded nanobubbles reduce cholesterol and atherosclerosis in vivo | European Heart Journal | Oxford Academic (oup.com)

Cyclodextrin incorporated silicone materials and their use as carriers for actives

today’s cyclodextrin is an innovation from WACKER (Amitabha MitraMegan GutmanChristian Hartman and Vera Popova) where cyclodextrins are part of a silicone composition creating articles for absorption, encapsulation and delivery of actives and other compounds. Example of such articles could be transdermal patches, PSAs, medical device, membranes, gels, clothing or other wearable materials, etc. The invention can be used for various applications including cosmetics, medical, home care, textiles, industrial and others.

WO2023208316 CYCLODEXTRIN INCORPORATED SILICONE MATERIALS AND THEIR USE AS CARRIERS FOR ACTIVES (wipo.int)