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,

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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

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

drug delivery, Today's cyclodextrin,


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


Dóra Ujj presentation at the Therapeutical Purposes Research and Development Congress at the University of Debrecen

drug delivery

Dóra Ujj (Budapest University of Technology and Economics) presents the results of her collaboration with Milo Malanga Ph.D., Szabolcs Béni, Gábor Benkovics Ph.D. and Tamas Sohajda, among others on analytical and therapeutic applications of Sugammadex analogs at the Therapeutical Purposes Research and Development congress at University of Debrecen.
Thank you for the great organization, if you are close, you should try to attend the 2nd day of the even today with more lectures on cyclodextrin, drug delivery, and pharmaceutical technology.

If you are interested in the details, you can also read the paper published on the topic.

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

drug delivery, Today's cyclodextrin,

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 Patil, Vasudha Prithipaul, Aaron Muth & Nitesh Kunda 

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