Significant progress in the development of new nanomedicines
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Significant progress in the development of new nanomedicines

© Adeline Deward – Illumine – www.illuminescience.be

Nanomedicine represents a revolutionary advance in the field of pharmaceuticals, offering promising prospects for the treatment of various diseases. At the nanoscale, these drugs demonstrate increased efficacy, allowing precise targeting of diseased cells and minimizing side effects. Thanks to their reduced size, nanomedicines can more easily overcome biological barriers, improving their ability to reach specific areas of the body. Nanomedicines also help improve the bioavailability of drugs, thereby prolonging their duration of action. This characteristic is critical for the treatment of chronic diseases that require regular medication.

Nanomedicines represent a revolutionary advance in the field of pharmaceuticals, offering promising prospects for the treatment of various diseases. At the nanoscale, these drugs demonstrate increased effectiveness, allowing precise targeting of diseased cells and minimizing side effects. Thanks to their reduced size, nanomedicines can more easily overcome biological barriers, improving their ability to reach specific areas of the body. Nanomedicines also help improve the bioavailability of drugs, thereby prolonging their duration of action. This characteristic is critical for the treatment of chronic diseases that require regular medication.

These nanomedicines, ten to one hundred times smaller than a cell, encapsulate active molecules to protect them from degradation in the blood and control their transport in space and time to an organ, diseased tissue or cell.

Today, the biomedical sector has a relatively large arsenal of nanovectors for drug delivery. The most commonly used nanovectors are liposomes, small spherical particles composed of a bilayer of lipids that envelop various drugs to be delivered into the body.

When these so-called first-generation lipid nanovectors are introduced into the bloodstream, opsonin-type proteins attach to their walls. The so-called “opsonized” nanovector is then recognized by macrophage receptors in the liver, leading to its rapid degradation. This significantly reduces the persistence of nanovectors in the blood and reduces their effectiveness.

Therefore, to circumvent this problem, the surface of nanovectors is usually “decorated” with a synthetic polymer called polyethylene glycol (PEG). These second-generation nanovectors, called “PEGylated,” will no longer be “modified” with opsonins. They are no longer captured and degraded by liver macrophages and remain in the circulation much longer.

Despite the stealth it provides to nanovectors, PEG, however, has serious drawbacks that limit their effectiveness. Indeed, PEG does not allow nanovectors to be effectively taken up by target cells and release the active molecule after entering the cell. Moreover, PEG can be recognized by the immune system and lead to the production of anti-PEG antibodies, which can cause an unwanted and exacerbated immune response. This is called the PEG dilemma.

In recent years, nanomedicine research has actively focused on the development of new polymers alternative to PEG. The goal is to maintain latent properties similar to those of PEG while improving cell penetration and release of the active molecule, and limiting immunogenicity.

It is for this purpose that 3 research laboratories work with complementary skills in the fields of chemistry (Dr. Antoine Debugne, research unit of CESAM – CERM), pharmaceuticals (Prof. Géraldine Peel, LTBP – CIRM) and biology (Dr. Denis Mottet, MAGE) . Laboratory – GIGA Institute) led an interdisciplinary research project called LIPEGALT, funded in 2019 under the Agreed Research Action (ARC) of the University of Liège.

At the end of 4 years of research, the work of this collaborative program demonstrated that two new families of polymers, poly(N-vinylpyrrolidone) and poly(N-methyl-N-vinylacetamide), can be considered as viable alternatives to the use of PEG in the development of new nanomedicines. Indeed, these two polymers are very poorly immunogenic compared to PEG and have no toxicity to a living organism. In addition, compared to PEG, poly(N-methyl-N-vinylacetamide) grafted onto lipid nanovectors improves their penetration into cells and provides better intracellular release of the encapsulated active molecule.

The results of this research led to the publication of scientific articles in relevant scientific journals such as the Journal of Controlled Release (JCR) and Advanced Healthcare Materials. The journal Advanced Healthcare Materials has just highlighted this research, illustrating it in Lid its latest periodical (illustration © Adeline Deward – Illumine – www.illumininescience.be).

The original and innovative side of this work, and in particular the synthesis and use of polymers of the Poly(N-methyl-N-vinylacetamide) type, made it possible to obtain a patent from the European Patent Office.

Another great example of fruitful interdisciplinary collaboration between different research centers in Houliège!

Recommendations

Poly(vinylpyrrolidone) derivatives as an alternative to PEG for latent, non-toxic and less immunogenic delivery of siRNA-containing lipoplex.
Berger M, Toussaint F, Jemaa SB, Laloy J, Pendeville H, Evrard B, Jerome S, Lechanter A, Mottet D, Debugne A, Pil J. J Control Release. September 2023; 361:87–101. doi: 10.1016/j.jconrel.2023.07.031. Epub Aug 2, 2023 PMID: 37482343

Poly(N-methyl-N-vinylacetamide): a potent alternative to PEG for lipid-based nanocarriers delivering siRNA.

Berger M, Toussaint F, Ben Jemaa S, Macoua E, Pendeville H, Evrard B, Jerome S, Leblond Chain J, Lechanter A, Mottet D, Debugne A, Pille J. Adv Healthc Mater. 2024 Mar;13(8):e2302712. doi:10.1002/adhm.202302712. Epub November 30, 2023 PMID: 37994483

Contacts

Denis Motte (GIGA)

Geraldine Peel (CIRM)

Antoine Debugne (CERM)

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