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.
While the mainstream use of CDs in pharma is solubilization, improving chemical stability is close to 2nd most popular, even though it is more complicated to achieve. This patent by Thorsteinn Loftsson (Oculis S.A.) and Zoltán Fülöp encorporates a nice case study of preventing the oxidation of corticosteroids.
See the full patent on PatentScope
A great compilation on the controlled drug delivery mediated by cyclodextrin-based supramolecular self-assembled carriers: From design to clinical performances at Pharma Excipients International AG compiled by University POLITEHNICA of Bucharest (Jana Ghitman and Voicu Stefan Ioan)
Fresh from the oven of the Francesco Trotta and Adrián Matencio Durán (Università degli Studi di Torino) lab, two papers on the uses of hyper-branched CD-polymer:
No 1: use as an anticoagulant, which is a very innovative application for CDs that are getting more and more spotlight
No 2: use as transfection promoters of plasmids.
I congratulate you on this ambitious research goal, loved both papers and look forward to seeing from sprouting from the collaboration you recently started with CarboHyde!
Yousef Khazaei monfared, Mohammad Mahmoudian, Claudio Cecone, Fabrizio Caldera, Sanya Haiaty, Reza Rahbarghazi, Parvin Zakeri-Milani, Gjylije Hoti, Fabrizio Caldera, Roberta Cavalli
This novel application is a fascinating combination of tumor targeting and diagnosis using of 68Ga-labelled cyclodextrin for positron emission tomography of PGE2-positive tumors.
University of Debrecen – Gabor Opposits, István Jószai, Istvan Kertesz, Zita Képes, Méhes Gábor, Ferenc Fenyvesi István Hajdu, György Trencsenyi
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.
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.
