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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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)

Molecular Mind Games: The Medicinal Action of Cyclodextrins in Neurodegenerative Diseases

carbohydrates, ,

Cyclodextrins are often used as molecular carriers for small active ingredients in the medicine. Recently, the intrinsic medicinal activity of some of these compounds has been under investigation, mainly related to their ability to interfere with cholesterol and, therefore, prevent and treat cholesterol-related diseases such as cardiovascular disease and neuronal diseases arising from altered cholesterol and lipid metabolism. One of the most promising compounds within the cyclodextrin family is 2-hydroxypropyl-β-cyclodextrin (HPβCD), owing to its superior biocompatibility profile. This work presents the most recent advances in the research and clinical use of HPβCD against Niemann–Pick disease, a congenital condition involving cholesterol accumulation inside lysosomes in brain cells, Alzheimer’s and Parkinson’s. HPβCD plays a complex role in each of these ailments, going beyond the mere sequestering of cholesterol molecules and involving an overall regulation of protein expression that helps restore the normal functioning of the organism.
Fantastic review by Susana Santos Braga form Universidade de Aveiro

See the full article here: Molecular Mind Games: The Medicinal Action of Cyclodextrins in Neurodegenerative Diseases

IgG N-Glycosylation Is Altered in Coronary Artery Disease

carbohydrates, ,

Coronary artery disease (CAD) is the most common cardiovascular disease, and previous studies have shown a significant association between N-glycosylation and the development of atherosclerotic plaques. Genos Ltd, Sveučilište u Rijeci / University of Rijeka and University of Zagreb/Sveuciliste u Zagrebu teamed up to determine whether the N-glycome of immunoglobulin G is associated with the disease as N-glycans are known to alter the effector functions of IgG, which may enhance the inflammatory response.
The most notable differences were observed in women, where the presence of sialylated N-glycan structures was negatively associated with CAD. The obtained data provide insight into the IgG N-glycome composition in CAD as well as the biomarker potential of IgG N-glycans in CAD.
Barbara Radovani, Frano Vučković, Aldo Pietro Maggioni, Ele Ferrannini, Gordan Lauc and Ivan Gudelj

See the full article here

Disease management to disease modification – removing plaque to undo atherosclerosis

Today's cyclodextrin, ,

You can read a great interview with folks from Cyclarity Therapeutics at Longevity.Technology. Since they are one of the few companies developing tailor-made CDs to tackle a major disease, this is certainly worth attention.
“Cyclarity’s approach to true disease medication, and therefore reversal of age-related disease, without doubt, offers a great deal of promise for investors, for healthcare systems in the US and globally, and most of all for those affected by the atherosclerosis-related disease.
. . . this may be the perfect opportunity for Cyclarity to enter the field, as it is one of the few solutions available that addresses the limiting factors of previous therapies both from a scientific perspective and from a market perspective.”

See the full article here

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.

See the full article here

Cyclodextrin boostered-high density lipoprotein for antiatherosclerosis by regulating cholesterol efflux and efferocytosis

drug delivery, drug development,

The cyclodextrin-supported atherosclerosis treatment field is getting crowded. Here is a unique approach using polyethylene glycol succinate (TPGS)-CD, which was adsorbed on rHDL, then modified with Apo-Ai, and coated with hyaluronan to obtain HT-rHDL. Piece of cake!
China Pharmaceutical University

Full article on ScienceDirect
https://doi.org/10.1016/j.carbpol.2022.119632

cholesterol, carbohyde