Comparative investigation of pulmonary vasodilating effects of inhaled Nitric Oxide (NO) gas therapy and inhalation of SIN-1, a new drug formulation containing an NO-donor metabolite

drug delivery, Today's cyclodextrin, ,

Today’s cyclodextrin is a nice collaborative formulation and in vivo (porcine) study between Semmelweis University and Cyclolab R&D Ltd.
In the project, the hemodynamic effect of inhalative SIN-1a (the unstable active metabolite of molsidomine, stabilized by cyclodextrine) was studied. The pulmonary vasodilator effect of SIN-1 was dose dependent, and in case of larger dose it was comparable to that of iNO. However, the vasodilatory effects of SIN-1 inhalation was not limited to the pulmonary circulation, a significant and dose-dependent systemic vasodilation could also be documented.
My only regret here is not all contributors met the authors’ list finally.

Comparative investigation of pulmonary vasodilating effects of inhaled Nitric Oxide (NO) gas therapy and inhalation of SIN-1, a new drug formulation containing an NO-donor metabolite | European Heart Journal | Oxford Academic (oup.com)

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Development of α-Cyclodextrin-Based Orally Disintegrating Tablets for 4-Phenylbutyrate

drug delivery, Today's cyclodextrin

Today’s cyclodextrin:
One of the greatest features of CDs is that with a proper application (especially when the local CD concentration is relatively high), they can not only improve the solubility but also the permeability of compounds. For example, in the case of a peroral application, let’s say an orally disintegrating tablet. Not to mention that their taste masking potential is also of use in this case. 3 birds with one stone!

In this paper, you can find a great example of such a smart application. If you are interested in developing similar formulations, check out the first steps here: Formulation development – www.carbohydesolutions.com

Pharmaceutics | Free Full-Text | Development of α-Cyclodextrin-Based Orally Disintegrating Tablets for 4-Phenylbutyrate (mdpi.com)

Development of abiraterone acetate tablets with enhanced oral bioavailability

drug delivery, Today's cyclodextrin

Today’s cyclodextrin
Reading this paper from Yeungnam University by Jong Oh Kim et al reminded me about a core application of CD’s: improving oral bioavailability of compounds. While this feature does not work generally on all compounds, it certainly does on the ones, where the poor solubility is the main cause of the low oral bioavailability. On the other hand, this feature of CD’s often make developing generic drugs with this excipients impossible, while creating improved/added value reformulations of repurposed APIs remains a target use.

If you have projects like this on your table, you might find it useful to check this website: Development of abiraterone acetate tablets with enhanced oral bioavailability | Journal of Pharmaceutical Investigation (springer.com)

Cyclodextrin-loaded nanobubbles reduce cholesterol and atherosclerosis in vivo

drug delivery, ,

While the uses of cyclodextrin as active ingredients is emerging both by the number of target diseases, companies developing them and types of CDs used, their efficient delivery remains a challenge.
The nanobubbles presented here could incorporate the CDs, accumulate in the atherosclerotic lesions, the release of CD and the reduce the total plaque area in the entire aorta and eventually reduce cholesterol level in mice plasma.
Cyclodextrin-loaded nanobubbles reduce cholesterol and atherosclerosis in vivo | European Heart Journal | Oxford Academic (oup.com)

Cyclodextrin incorporated silicone materials and their use as carriers for actives

drug delivery, Today's cyclodextrin,

today’s cyclodextrin is an innovation from WACKER (Amitabha Mitra, Megan Gutman, Christian Hartman and Vera Popova) where cyclodextrins are part of a silicone composition creating articles for absorption, encapsulation and delivery of actives and other compounds. Example of such articles could be transdermal patches, PSAs, medical device, membranes, gels, clothing or other wearable materials, etc. The invention can be used for various applications including cosmetics, medical, home care, textiles, industrial and others.

WO2023208316 CYCLODEXTRIN INCORPORATED SILICONE MATERIALS AND THEIR USE AS CARRIERS FOR ACTIVES (wipo.int)

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

drug delivery, Today's cyclodextrin,

Today’s cyclodextrin is a smart and very practical study, highlighting how different cyclodextrins added to a liposomal formulation could influence the release of the active load.

The results demonstrated that the CDs effect on the membrane depends on the CD type, CD concentration, and membrane cholesterol content. The investigated CDs exhibited an instantaneous permeabilizing effect promoting vesicle leakage of API from the various membranes; this effect increased with CDs concentration. Among the studied CDs, α-CD, β-CD, and RAMEB were the most permeabilizing CDs on the different membranes.

Ghenwa Nasr, Helene Greige, Sophie Fourmentin, Abdelhamid ELAISSARI, Nathalie Khreich

BJOC – Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration (beilstein-journals.org)

Targeted delivery of oligonucleotides into eukaryotic cells using hybrid maltose/cyclodextrin polyplexes

drug delivery

Another great application using cyclodextrin in non-viral drug delivery for gene therapy is presented in this paper underlining the versatility of these compounds in this field – similar in application to what we are working on in GENEGUT.
Colleagues present a novel targeting bio-conjugate for selective delivery of therapeutic nucleic acids, including RNA oligonucleotides and DNA- oligonucleotides, preferably gene-encoding DNA plasmids or minicircle DNAs, to eukaryotic cells by means of receptor-mediated endocytosis and endosomal release.
Dietmar Appelhans et al.

WO2023169899 TARGETED DELIVERY OF OLIGONUCLEOTIDES INTO EUKARYOTIC CELLS USING HYBRID MALTOSE/CYCLODEXTRIN POLYPLEXES (wipo.int)

Preparation and evaluation of β-cyclodextrin-based nanosponges loaded with Budesonide for pulmonary delivery

carbohydrates, drug delivery, drug development,

Creating effective drug delivery systems for pulmonary applications is fascinating challenge. Recently, we have reported on the progress Aquilon Pharma made using cyclodextrins to deliver different APIs, their lead compounds being budasonide.
In this paper Francesco Trotta‘s and Aliasgar Shahiwala‘s groups proposes an alternative solution using cyclodextrin nanosponges. In vitro and in vivo studies showed almost complete drug release and drug absorption from the lungs in the initial 2 h for pure BUD, which were sustained up to 12 h from BUD loaded into nanosponges.

Preparation and evaluation of βcyclodextrin-based nanosponges loaded with Budesonide for pulmonary delivery – ScienceDirect

Nano-drug for actively targeting abdominal aortic aneurysm and preparation method thereof

drug delivery

Interesting drug delivery technology targeting abdominal aortic aneurysm by taking alpha-cyclodextrin as a skeleton and bonding a luminol unit. Afterwards, alendronate sodium, polyethylene glycol and lecithin are applied to modify a vascular calcification targeting unit on the surface of the #nanoparticle. The nano-drug is combined with pathological calcified blood vessels of the abdominal aortic aneurysm, so that the off-target effect caused by too high artery blood flow speed is reduced, the targeted enrichment effect on the abdominal aortic aneurysm is enhanced, the inflammatory microenvironment generated at the abdominal aortic aneurysm part can be more effectively inhibited, and the treatment effect of the abdominal aortic aneurysm is improved. The treatment effect of delaying the progress of the abdominal aortic aneurysm is achieved.

CN116271101A Nano-drug for actively targeting abdominal aortic aneurysm and preparation method thereof

Development of Liposome Systems for Enhancing the PK Properties of Bivalent PROTACs

carbohydrates, drug delivery,

Proteolysis-Targeting Chimeras (PROTACs) are a promising new technology in drug development. They have rapidly evolved in recent years, with several of them in clinical trials. While most of these advances have been associated with monovalent protein degraders, bivalent PROTACs have also entered clinical trials, although progression to market has been limited. One of the reasons is the complex physicochemical properties of the heterobifunctional PROTACs. A promising strategy to improve pharmacokinetics of highly lipophilic compounds, such as PROTACs, is encapsulation in liposome systems. Here liposome systems for intravenous administration to enhance the PK properties of two bivalent PROTAC molecules are described, by reducing clearance and increasing systemic coverage. A PROTAC-in-cyclodextrin liposome system was developed where the drug was retained in the liposome core. In PK studies at 1 mg/kg for GNE-01 the PROTAC-in-cyclodextrin liposome, compared to the solution formulation, showed a 80- and a 380-fold enhancement in AUC for mouse and rat studies, respectively. We further investigated the same PROTAC-in-cyclodextrin liposome system with the second PROTAC (GNE-02), where we monitored both lipid and drug concentrations in vivo. Similarly, in a mouse PK study of GEN-02, the PROTAC-in-cyclodextrin liposome system exhibited enhancement in plasma concentration of a 23× increase over the conventional solution formulation. Importantly, the lipid CL correlated with the drug CL. Additionally, we investigated a conventional liposome approach for GNE-02, where the PROTAC resides in the lipid bilayer. Here, a 5× increase in AUC was observed, compared to the conventional solution formulation, and the drug CL was faster than the lipid CL. These results indicate that the different liposome systems can be tailored to translate across multiple PROTAC systems to modulate and improve plasma concentrations. Optimization of the liposomes could further improve tumor concentration and improve the overall therapeutic index (TI). This delivery technology may be well suited to bring novel protein targeted PROTACs into clinics.
This is a unique industrial collaboration between Genentech, Arvinas & Bristol Myers Squibb.
#cyclodextrin #liposome #drugdelivery

Pharmaceutics | Free Full-Text | Development of Liposome Systems for Enhancing the PK Properties of Bivalent PROTACs (mdpi.com)