Grafting of Cyclodextrin to Theranostic Nanoparticles Improves Blood-Brain Barrier Model Crossing

drug delivery,

today’s cyclodextrin:
Core–shell superparamagnetic iron oxide nanoparticles hold great promise as a theranostic platform in biological systems. Antonino Puglisi and coworkers report the biological effect of multifunctional cyclodextrin-appended SPIONs (CySPION) in mutant Npc1-deficient CHO cells compared to their wild-type counterparts. CySPIONs show negligible cytotoxicity while they are strongly endocytosed and localized in the lysosomal compartment. Through their bespoke pH-sensitive chemistry, these nanoparticles release appended monomeric cyclodextrins to mobilize over-accumulated cholesterol and eject it outside the cells. CySPIONs show a high rate of transport across blood–brain barrier models, indicating their promise as a therapeutic approach for cholesterol-impaired diseases affecting the brain.

University of Natural Resources and Life Sciences, Vienna (BOKU): Peter van Oostrum, Erik Reimhult
Università degli Studi di Catania: Noemi Bognanni, Graziella Vecchio
Ege University: Ece Bayir
University of Oxford: Dawn Shepherd, Frances Platt

See the full article here: Grafting of Cyclodextrin to Theranostic Nanoparticles Improves Blood-Brain Barrier Model Crossing

Confocal micrographs of Npc1-deficient CHO after incubation with 0.1 mg/mL FITC-CySPION for 72 h showing co-localization, with Pearson’s coefficient of 0.37, between FITC-CySPION (green) and LysoTracker Deep Red within the lysosomal compartments (red) within the ROI preproduced on the right. The used excitation wavelengths and fluorescence maxima are indicated in the figures. The field of view is 290 × 290 µm2.

Oligonucleotide Formulations Prepared by High-Speed Electrospinning: Maximizing Loading and Exploring Downstream Processability

drug delivery

today’s cyclodextrin:
is about developing antisense oligonucleotide tablet formulations using high-speed electrospinning. Hydroxypropyl-beta-cyclodextrin (HPβCD) was used as a stabilizer and an electrospinning matrix from one of the best pharma groups in Hungary (FirePharma Research Group BME – Budapest University of Technology and Economics) collaborating with Janssen Inc.

The fibrous HPβCD–antisense oligonucleotide formulations showed no sign of physical or chemical degradation over the 1-year stability study, which also shows the suitability of the HPβCD matrix for the formulation of biopharmaceuticals. The obtained results demonstrate possible solutions for the challenges of electrospinning, such as scale-up and downstream processing of the fibers.

Edit Hirsch, Márió Nacsa, Edina Szabó, Panna Vass, Julia Domjan, Attila Farkas,Zsuzsanna Eke, Tamás Vigh, Sune Klint Andersen, Geert Verreck, György Marosi and Zsombor Kristof Nagy et al

See the full article here: Oligonucleotide Formulations Prepared by High-Speed Electrospinning: Maximizing Loading and Exploring Downstream Processability


An Engineered Nanosugar Enables Rapid and Sustained Glucose-Responsive Insulin Delivery in Diabetic Mice

carbohydrates, drug delivery

Glucose-responsive insulin-delivery platforms sensitive to dynamic glucose concentration fluctuations and providing both rapid and prolonged insulin release have great potential to control hyperglycemia and avoid hypoglycemia diabetes. RMIT University and Monash University present biodegradable and charge-switchable phytoglycogen nanoparticles capable of glucose-stimulated insulin release. The nanoparticles are “nanosugars” bearing glucose-sensitive phenylboronic acid groups and amine moieties that allow effective complexation with insulin (≈95% loading capacity) to form nano complexes. A single subcutaneous injection of nano complexes shows a rapid and efficient response to a glucose challenge in two distinct diabetic mouse models, this results in optimal blood glucose levels for up to 13 h. The nano complexes’ morphology is key to controlling rapid and extended glucose-regulated insulin delivery in vivo. These studies reveal that the injected nano complexes enabled efficient insulin release in the mouse, with optimal bioavailability, pharmacokinetics, and safety profiles. These results highlight a promising strategy for the development of a glucose-responsive insulin delivery system based on natural and biodegradable nano sugar.
Rong XU, Sukhvir Kaur Bhangu, Karly Sourris, Domitilla Vanni, Marc-Antoine Sani, Karen Alt, Be’eri Niego, Dr. Quinn A. Besford, Brendan Dyett, Irena (Iśka) Carmichael, Mark Cooper, Christoph Hagemeyer, Francesca Cavalieri, et al

See the full article here: An Engineered Nanosugar Enables Rapid and Sustained Glucose-Responsive Insulin Delivery in Diabetic Mice

Thiolated cyclodextrins: A comparative study of their mucoadhesive properties

drug delivery, Today's cyclodextrin

today’s cyclodextrin:
when it comes to CDs, mucoadhesive properties are rarely in focus. But why not?
Andreas Bernkop-Schnürch’s team at Leopold-Franzens Universität Innsbruck investigated the mucoadhesive properties of nonionic, negatively, and positively charged thiolated cyclodextrins (CDs), including α-, β-, and γ-CDs of the low and high degree of thiolation.
In conclusion, a high degree of thiolation and the introduction of cationic charges are mainly responsible for the high mucoadhesive properties of CDs and generate, GCD derivatives do better in this aspect.

See the full article here: Thiolated cyclodextrins: A comparative study of their mucoadhesive properties

A mannosylated polymer with endosomal release properties for peptide antigen delivery

drug delivery, ,

The University of Washington introduces Man-VIPER, a self-assembling, pH-sensitive, mannosylated polymeric peptide delivery platform that targets dendritic cells in the lymph nodes, encapsulates peptide antigens at physiological pH and facilitates the endosomal release of antigens at acidic endosomal pH through conjugated membranolytic peptide melittin. In vivo, the Man-VIPER polymer demonstrated an adjuvant effect and induced the proliferation of antigen-specific cytotoxic T cells and helper T cells compared to free peptides and Man-AP. The antigen delivery with Man-VIPER-NR generated significantly more antigen-specific cytotoxic T cells than Man-VIPER-R in vivo. and Man-VIPER-NR exerted superior efficacy in a B16F10-OVA tumor model. These results highlight Man-VIPER-NR as a safe and powerful peptide cancer vaccine platform for cancer immunotherapy.

Dinh Chuong (Ben) Nguyen, Tran Luu, Omeed Yazdani, Patrick Stayton and Suzie Pun

See the full article here: A mannosylated polymer with endosomal release properties for peptide antigen delivery

Veklury® (remdesivir) formulations inhibit initial membrane-coupled events of SARS-CoV-2 infection due to their sulfobutylether-β-cyclodextrin content

carbohydrates, drug delivery,

It has always been a bit of a mystery that given the antiviral effect of certain cyclodextrin, we can attribute all the antiviral effect of Veklury to remdesivir, which takes 3% of the formulation or maybe SBECD (97% of the formulation) also has some role. Researchers from University of Debrecen explore those questions.
Veklury® and different cholesterol-depleting cyclodextrins (CDs) reduced the binding of the spike receptor binding domain to ACE2 and spike trimer internalization for Wuhan-Hu-1, Delta, and Omicron variants. Correlations of these effects with cholesterol-dependent changes in membrane structure and decreased, lipid raft-dependent ACE2-TMPRSS2 interaction establish that SBECD is not simply a vehicle but also an effector in Veklury® due to its cholesterol-depleting potential.
Gyorgy Panyi, Florina Zakany et al.

See the full article here.

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

drug delivery, ,

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 Vincze, Facskó Réka, Budai-Szűcs Mária, Gábor Katona, Benjámin Gyarmati, Anita Csorba, Dr. Zelkó Romána, Zoltán Zsolt Nagy, Lajos Szente, György Tibor Balogh,

See the full article here.

Cyclodextrin-Based Nanoparticles for Delivery of Antisense Oligonucleotides Targeting Huntingtin

drug delivery, ,

Check out the most recent paper of our collaborators in the GENEGUT Horizon Europe consortia presenting cyclodextrin-based nanoparticles for delivery of antisense oligonucleotides targeting huntingtin. Even if we were not part of this story, we are proud to get involved in the next chapter!

University College Cork – Monique Culturato Padilha Mendonça, PhD, Caitriona O’Driscoll et al
APC Microbiome Ireland – John Cryan

See the full article here