Controlled drug delivery mediated by cyclodextrin-based supramolecular self-assembled carriers: From design to clinical performances

today’s #cyclodextrin:
achieving controlled release with cyclodextrins can be really challenging, yet it is doable. In fact, there are multiple strategies to get there. In this review, Jana Ghitman and Voicu Stefan Ioan collected different approaches of cyclodextrins-based drug delivery forms that are suitable for co-delivery systems, non-viral vectors for gene delivery, and theranostics.
This review presents the latest achievements in nanoparticle-based supramolecular architectures, taking into account the main synthesis methods and the stimuli that control the release (light-responsive, pH-responsive, redox-responsive, and multi-responsive). The review also presents applications and also the present status regarding commercial systems based on cyclodextrins and their characteristics.

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Controlled drug delivery mediated by cyclodextrin-based supramolecular self-assembled carriers: From design to clinical performances

Cyclodextrin-enabled nepafenac eye drops with improved absorption open a new therapeutic window

This research is close to my heart as it comes from a Hungarian collaboration on developing nepafenac eyedrops with improved absorption. The results showed that one formulation possessed better bioavailability ex vivo than Nevanac® 0.1 % suspension, while the other formulation containing only 60 % of the original dose was ex vivo equivalent with Nevanac® opening the way to nepafenac-containing eye drops with better patient compliance in the future.

Anna VinczeFacskó RékaBudai-Szűcs MáriaGábor KatonaBenjámin GyarmatiAnita CsorbaDr. Zelkó Romána, Zoltán Zsolt Nagy, Lajos SzenteGyörgy Tibor Balogh,

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Formulation, composition or foodstuff additives for the modification of glycemic response methods of manufacturing and using the same 

The story of two stone and one bird:
It is very rare that different cyclodextrins are combined in the same formulation, but there are examples on the market. Hoow Foods‘s invention uses one CD which hides the unpleasant taste of any phenylpropanoid from the sensory receptors. This will have the added advantage that the phenylpropanoids will be protected from the acidic environment of the stomach allowing more of them to reach the intestines. Adding a second cyclodextrin that has not been complexed makes the composition behave similarly to known sugars and starches thereby minimising any effect on the texture of the foods to which it is added.

See the full patent on Espacenet

Aldeyra Therapeutics Announces FDA Acceptance of New Drug Application for Reproxalap for the Treatment of Dry Eye Disease

This is a long-awaited approval of the very first SBECD-enabled reproxalap ophthalmic formulation delivered by Aldeyra Therapeutics to treat dry eye disease.
Reproxalap, an investigational new drug candidate, is a first-in-class small-molecule modulator of RASP (reactive aldehyde species), which are elevated in ocular and systemic inflammatory disease. The mechanism of action of reproxalap has been supported by the demonstration of statistically significant and clinically relevant activity in multiple physiologically distinct late-phase clinical indications.
Dry eye disease is a common inflammatory disease estimated to affect 39 million or more adults in the United States. The disease is characterized by insufficient moisture and lubrication in the anterior surface of the eye, leading to dryness, inflammation, pain, discomfort, irritation, diminished quality of life, and in severe cases, permanent vision impairment. Among many physicians and patients, existing therapy for dry eye disease is generally regarded as inadequate and often requires weeks or months to demonstrate activity. In patients with dry eye disease, RASP may contribute to ocular inflammation, diminished tear production, ocular redness, and changes in tear lipid composition. By diminishing RASP levels, Aldeyra’s lead RASP modulator reproxalap represents a novel and differentiated approach for treating the symptoms and signs of dry eye disease.

See the full press release here

Solubility Enhancement and Inhalation Delivery of Cyclodextrin-Based Inclusion Complex of Delamanid for Pulmonary Tuberculosis Treatment

Pulmonary formulations are a relatively new and upcoming area for cyclodextrins without any marketed product to date. Still, due to covid, these applications came more into focus and should be studied extensively.
Delamanid (DLD), an antituberculosis drug, has poor aqueous solubility, and in this study, we aim to improve its solubility using cyclodextrin complexation. In bacterial studies, the minimum inhibitory concentration of the DLD-CD complex was significantly reduced (four-fold) compared to free DLD. Furthermore, accelerated stability studies confirmed that the inclusion complex was stable for 4 weeks with 90%w/w drug content.

St. John’s University – Suyash PatilVasudha PrithipaulAaron Muth & Nitesh Kunda 

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Voriconazole Eye Drops: Enhanced Solubility and Stability through Ternary Voriconazole/Sulfobutyl Ether β-Cyclodextrin/Polyvinyl Alcohol Complexes

This is a wonderful example of how something known (voriconazole-CD formulation) could be turned into something innovative. Researchers from Chulalongkorn University and Iceland University developed voriconazole eyedrops which shows high mucoadhesion, sustained release, good ex vivo permeability through the porcine cornea, and no sign of irritation. The stability study revealed that VCZ eye drops provide a shelf-life of more than 2.5 years at room temperature, while a shelf-life of only 3.5 months was observed for the extemporaneous Vfend® eye drops.

Hay Man Saung Hnin SoeKhanittha KerdpolThorsteinn Loftsson Phatsawee Jansook et al

Use cyclodextrins as a radiostabilizer

Using CDs to stabilize drugs chemically is rather frequently used. But did you know that they can also be used to stabilize radiopharmaceuticals? According to the patent of GE HealthCare (Kristine Opsvik Wikene; Kahn Imtiaz Ahmed; Graeme McRobbie) combined with a radiostabilizer (like ascorbic acid), a cyclodextrin as co-stabilizer improves the stability of radiopharmaceuticals compared to using a conventional stabilizer.

See the full patent on Espacenet.

Methyl-BCD is used in antibody-drug conjugate

An interesting application is highlighted in the patent of RemeGen荣昌生物: methyl-BCD is used in antibody-drug conjugate formulations where the primary benefit is that ADC dose can be lowered (due to higher efficacy), which leads to mitigating safety concerns lowering costs, and patient treatment costs. Fascinating, huh? (Figure: Araris Biotech AG)

See the full patent on Espacenet.