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


The Bicyclos International Workshop will be held in Budapest from September 24th to September 26th.

The workshop is open to all R&I personnel from both public and private sectors who are interested in carbohydrate research, especially cyclodextrins. On September 24-25, there will be seminars on the sustainable synthesis of carbohydrates and their derivatives, including their characterization and application in devices. The following days, September 25-26, will cover topics such as launching a spinoff company, with seminars by experts from CarboHyde and Cyclarity Therapeutics, and guidance on writing an MSCA proposal, featuring sessions led by coordinators of MSCA projects, which will also include practical exercises.

Register here: Bicyclos International Workshop on September 24-26, 2024

A registration fee of 225 Euro applies and comprises participation in the event, digital copies of the seminar slides, lunches on 24-25 September, and coffee breaks on 24-25-26 September. Registration fees do not apply to Bicyclos staff members.

The deadline for registration is May 31, 2024

The detailed program can be read here

Mirror-image cyclodextrins

today’s cyclodextrin:
Do you often take a good look in the mirror?

Nobel laureate Sir Fraser Stoddard, Daniel W. Armstrong, and their team report the syntheses of three mirror-image CDs—namely, α-, β- and γ-L-CDs, which are composed of six, seven and eight α-1,4-linked L-glucopyranosyl residues, respectively.

The availability of L-CDs has enabled the elucidation of an unprecedented chiral self-sorting of a racemic modification of β-CDs in the solid state and an investigation of the chiral recognition of enantiomeric fenchone by α-L-CD. This research identifies a missing piece of the cyclodextrin jigsaw and sets the stage for scientists to explore the mirror-image world of naturally occurring CDs.

Mirror-image cyclodextrins | Nature Synthesis

2024’s New FDA Drug Approvals


🌟 Discover the latest from the FDA’s CDER: 9 innovative drugs for Q1!
🧴Berdazimer (Zelsuvmi) tackles topical molluscum contagiosum with nitric oxide release.
💉Cefepime/enmetazobactam (Exblifep) combines forces for urinary tract infection relief.
💉LetibotulinumtoxinA (Letybo) smooths glabellar lines with botulinum neurotoxin.
💉Tislelizumab (Tivembra) fights esophageal squamous cell carcinoma with PD-1 mAb technology.
💊Resmetirom (Rezdiffra), a thyroid hormone receptor beta agonist, battles nonalcoholic steatohepatitis.
💊Aprocitentan (Tryvio) manages hypertension through endothelin receptor antagonism.
💊Givinostat (Duvyzat) aims at Duchenne muscular dystrophy with HDAC inhibition.
💉Sotatercept (Winrevair), an activin inhibitor, offers hope for pulmonary arterial hypertension patients.
💊Vadadustat (Vafseo) addresses CKD-related anemia in dialysis patients as an oral HIF-PH inhibitor.

Explore these groundbreaking treatments! Our appreciation to Chris De Savi for the great compilation!

METHOD FOR THE PRODUCTION OF LARGE-RING CYCLODEXTRINS

Today’s cyclodextrin is a great patent on unusual CDs: large-ringed ones. The systematic experimental study of the properties of the large-ring cyclodextrins (LR-CDs) as host systems was hampered for a long time by the inability to obtain individual LR-CDs in quantities necessary for experimental examinations. Breakthrough in the situation was a recent patent and reports of Sophie Beeren and coworkers from DTU – Technical University of Denmark

Now we have a scalable method, and the isolation of the product does not require chromatography. And what should we do with these CDs? Let’s start by looking into analytical, biotech, and pharma applications. Then we shall see…

WO2024042228 METHOD FOR THE PRODUCTION OF LARGE-RING CYCLODEXTRINS (wipo.int)

Adenovirus formulation

This recent patent from our friend Tao Peng at Roquette on preserving an adenovirus vaccine with the help of cyclodextrins got us thinking about how CDs can be used in this area.


EP4338727 ADENOVIRUS FORMULATIONS (wipo.int)

In the context of vaccines, cyclodextrins can effectively encapsulate antigens, ensuring their protection from degradation and improving their immunogenicity. Cyclodextrins offer stability advantages to vaccines by preventing the degradation of labile vaccine components during storage and transportation. Furthermore, cyclodextrins can serve as adjuvants, potentiating the immune response triggered by vaccines. Their unique structure and interaction with the immune system enhance the recognition of antigens by immune cells, leading to an improved activation of both innate and adaptive immune responses. This adjuvant effect contributes to the development of robust and long-lasting immune protection against targeted pathogens. Owing to the distinctive attributes inherent to nanoparticles, their integration into vaccine formulations has assumed an imperative role. Through the encapsulation of vaccine antigens/adjuvants within cyclodextrin nanoparticles, the potency and stability of vaccines can be notably enhanced. In particular, the capacity of amphiphilic cyclodextrins to form nanoparticles through self-assembly without surfactants or co-solvents is a captivating prospect for their application as carrier systems for antigens. In conclusion, cyclodextrins present a promising platform for enhancing the efficacy and stability of vaccines. Their ability to encapsulate antigens, stabilize labile vaccine components and act as adjuvants demonstrates their potential to revolutionize vaccine formulation and delivery. Further research and development in this field will facilitate the translation of cyclodextrin-based vaccine technologies into practical and impactful immunization strategies, ultimately benefiting global health and disease prevention.

Induction of Exocytosis Rescues Lysosomal GM2 Accumulation in Tay-Sachs Disease

Tay-Sachs disease, a progressive neurodegenerative disorder caused by mutations in the HEXA gene, lacks effective treatment. This study explores the therapeutic potential of δ-tocopherol and hydroxypropyl-β-cyclodextrin, targeting lysosomal exocytosis in Tay-Sachs models. Results indicate significant lysosomal GM2 reduction, offering hope for future treatments.

Induction of Exocytosis Rescues Lysosomal GM2 Accumulation in Tay-Sachs Disease (hindawi.com)

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)


Methods for the treatment of chronic kidney disease

We are happy to announce the acceptance of a great patent from CarboHyde’s collaborator, Renatus, a pharmaceutical company focused on developing cyclodextrin-based cholesterol metabolism modulators. Renatus is a pharmaceutical company whose mission is to provide safe and effective treatment options for the treatment of numerous cholesterol-driven diseases such as chronic kidney disease, atherosclerosis, and Alzheimer’s diseases. The core technology of the company allows the normalization of cholesterol homeostasis by removal of excessive and toxic cholesterol within diseased cells without significant harmful effects on normal cells.

The lead asset RN-005 is a cholesterol metabolism modulator that has proven strong therapeutic efficacy in preclinical models of both diabetic kidney disease (DKD) and focal segmental glomerulosclerosis (FSGS) wherein dysregulated cholesterol metabolism causes progressive damage and loss of function in the kidney. The gamma-cyclodextrin oligomers are effective in cholesterol metabolism enhancement, cholesterol efflux, reducing inflammatory cytokine secretion, renal clearance of cholesterol, and/or reducing albuminuria. Therefore, the gamma-cyclodextrin oligomers can be used to treat or alleviate chronic kidney disease, symptoms thereof and/or complications related to chronic kidney disease.

Espacenet – METHODS FOR THE TREATMENT OF CHRONIC KIDNEY DISEASE

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)