Development and Characterization of Cyclodextrin-Based Nanogels as a New Ibuprofen Cutaneous Delivery System

Today's cyclodextrin

Topical drug delivery with CDs seems straightforward, even with the extra advantage that CDs can contribute not only as solubilizers but also as permeation enhancers. Still, despite cosmetics, very few products are on the market.
The nano gel concept by Università degli Studi di Firenze (Marzia Cirri, Giulia Nerli, Natascia Mennini, Francesca Maestrelli, and Paola Mura) may open some new doors in this area.

See the full article here.

Figure 1. Solubility studies of ibuprofen (IBU) at 25 °C in pH 7.4 phosphate buffer alone (green bar) or in the presence of increasing amounts of HPβCD (blue bars) or EPIβCD (red bars).

First Patient Enrolled in Phase 1 Study of MTX-110 (MAGIC-G1 Study) in Patients with Recurrent Glioblastoma

Today's cyclodextrin, , ,

Even though used in many formulations with CDs, new ones entering clinical trials are not often. Midatech Pharma PLC recently announced recruiting the first patient in the Phase 1 Study of MTX-110 for recurrent #glioblastoma (NCT 05324501). Midatech has previously reported encouraging results from a Phase I study of MTX110 in diffuse intrinsic pontine glioma (NCT03566199, NCT04264143), and a Phase I study of MTX110 in medulloblastoma is being undertaken. and recurrent medulloblastoma (NCT04315064).

MTX110 is a water-soluble form of a panobinostat-free base, achieved through complexation with hydroxypropyl-β-cyclodextrin (HPBCD), that enables convection-enhanced delivery (CED) at potentially chemotherapeutic doses directly to the site of the tumor. Panobinostat is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor). The currently available oral formulation of panobinostat lactate (Farydak®) is not suitable for the treatment of brain cancers owing to poor blood-brain barrier penetration and inadequate brain drug concentrations.

MTX110 is delivered directly into and around the patient’s tumor via a catheter system (e.g., CED or fourth ventricle infusions) to bypass the blood-brain barrier. This technique exposes the tumor to very high drug concentrations while simultaneously minimizing systemic drug levels and the potential for toxicity and other side effects.

MTX110 has been granted Orphan Drug and Fast Track designations by the FDA and Orphan Medicinal Product designation by EMA.

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Comparison of the Efficacy and Safety of Adamgammadex with Sugammadex for Reversal of Rocuronium-Induced Neuromuscular Block: Results of a Phase II Clinical Trial

drug development, drug discovery, , ,

The success of Sugammadex inspired several further cyclodextrin research, including the development of other antidotes and discovering “follow-up” compounds for the same indication. The most advanced candidate in this field is Adamgammadex (developed by Adamerck) with its efficacy recently compared to SGM in a Phase II trial lead by Sichuan University. Although it was used in 2-3 times higher concentrations, the previously reported adverse effects were not observed in this study, including anaphylaxis, haemorrhage, recurarization, abnormal basic vital signs, or lengthened QRS intervals and QT intervals. Adamgammadex was found to be effective for reversing rocuronium-induced neuromuscular block as sugammadex.

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Degree and distribution of substitution of hydroxypropyl-β-cyclodextrin in enantioselective liquid-liquid extraction and countercurrent chromatographic enantioseparation

Today's cyclodextrin,

Using CDs in enantioseparation is rather straightforward. On an analytical level. However, preparation is a completely different question. Potential solutions for this problem and the impact of CD types are explored in the study of Zhejiang University of Technology and Jiaxing University, discussing applications in CPC and liquid-liquid extraction.

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Beren Awarded Expedited Roadmap for Treatment of Homozygous Familial Hypercholesterolemia

drug development, , , , ,

Fascinating news from Beren Therapeutics:
Beren Awarded Expedited Roadmap for Treatment of Homozygous Familial Hypercholesterolemia
Beren’s novel lead asset, BRN-002, was awarded an Innovation Passport under the United Kingdom’s Innovative Licensing and Access Pathway (ILAP), for the reversal of atherosclerosis in patients with Homozygous Familial Hypercholesterolemia. The ILAP aims to accelerate the time to market for innovative medicines that address the needs of patients with life-threatening or seriously debilitating diseases.
“We are excited to begin work under ILAP and look forward to collaborating with other regulators, payors, and governments to expedite the development and identify and remove access barriers.” – commented Jason Camm, CEO. Jules Payne from HEART UK – The Cholesterol Charity added that “Significant unmet needs remain, and with this advancement, we are hopeful for a new treatment option that can truly alter the course of the disease for the children and patients living with HoFH.”
Beren Therapeutics, P.B.C. is currently in stealth.

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Formulations with reduced degradation of polysorbate

Today's cyclodextrin, ,

Using CDs to formulate proteins, dominantly to prevent aggregation is more or less known; there are CDs marketed for such uses (Roquette – Kleptose Biopharma) still, no product is on the market.
This patent from Genentech (Brian Connolly; Lydia Hamburg; Emily Holz) proposes another feature: when using CDs with monoclonal antibodies, degradation of polysorbates is also reduced.

Sulfobutylether-β-cyclodextrin: A functional biopolymer for drug delivery applications

drug delivery, Today's cyclodextrin

If you even used CDs, you probably are familiar with SBECD. In this review, there is a nice colleaction of this parenteral excipient’s current and potential future applications.

Rucha Kothawade, Ashwini Markad, Sagar Pardeshi, Prashant Chaudhari, Marcela Longhi, Namdev Dhas, Jitendra Naik, Mónica Cristina García, Dr. Chandrakantsing Pardeshi [Ph.D.]

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Fully Symmetric Cyclodextrin Polycarboxylates: How to Determine Reliable Protonation Constants from NMR Titration Data

carbohydrates,

We are happy to share the most recent paper of Milo Malanga Ph.D. on acid-base properties of cyclodextrin, particularly Sugammadex and its analogs developed together with Semmelweis University (Szabolcs Béni, Eszter Kalydi), Richter Gedeon Nyrt. / Magyarország (Zoltán Szakács), Gábor Benkovics PhD and Dóra Ujj.
The pH-dependent charge of these compounds can now be accurately calculated in support of designing new analytical methods to exploit their charge-dependent molecular recognition, such as in cyclodextrin-aided chiral capillary electrophoresis.


Cyclodextrins: Only Pharmaceutical Excipients or Full-Fledged Drug Candidates?

Today's cyclodextrin, , , , ,

What is the future of cyclodextrin: excipient or API?
A very timely review from University of Debrecen (Gyorgy Panyi, Florina Zakany, et al.) discussing #molecular targets, mechanism of action, and ongoing research in several diseases. Which do you think holds the future?

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