Major breakthrough in the development of new nanomedicines
Nanomedicines represent a revolutionary advance in the pharmaceutical field, offering promising prospects for the treatment of various diseases. At the nanoscale, these drugs offer enhanced efficacy, enabling precise targeting of diseased cells while minimizing adverse effects. Thanks to their smaller size, nanomedicines can cross biological barriers more easily, enhancing their ability to reach specific sites in the body. Nanomedicines also help improve the bioavailability of drugs, prolonging their duration of action. This is crucial for the treatment of chronic diseases requiring regular drug administration.
These nanomedicines, ten to a hundred times smaller than a cell, encapsulate active molecules to protect them from degradation in the bloodstream, and control their transport in space and time to the diseased organ, tissue or cell.
Today, the biomedical sector has a relatively vast arsenal of nanovectors for drug delivery. The most frequently used nanovectors are liposomes, small spherical particles consisting of a double layer of lipids which envelop the various drug substances to be delivered to the body.
When these first-generation lipid nanovectors are injected into the bloodstream, ospsonin-type proteins bind to their walls. The "opsonized" nanovector is then recognized by macrophage receptors in the liver, which rapidly degrade it. This significantly reduces the persistence of nanovectors in the blood, compromising their efficacy.
To avoid this problem, nanovectors are commonly "decorated" with a synthetic polymer called polyethylene glycol (PEG). These second-generation "PEGylated" nanovectors are no longer susceptible to "modification" by opsonins. They are no longer captured and degraded by liver macrophages, and remain much longer in the bloodstream.
Despite the stealth it brings to nanoparticles, PEG has major drawbacks that limit their effectiveness. PEG does not allow nanovectors to be efficiently captured by target cells, and to release the active molecule after cell penetration. In addition, PEG can be recognized by the immune system, leading to the production of anti-PEG antibodies that can trigger an undesirable and exacerbated immune response. This is known as the PEG dilemma.
In recent years, research in the field of nanomedicines has actively focused on the development of new alternative polymers to PEG. The aim is to retain stealth properties similar to PEG, while improving cell penetration and active molecule release, and limiting immunogenicity.
With this objective in mind, 3 research laboratories with complementary skills in the fields of chemistry (Dr. Antoine Debuigne, CESAM Research Unit - CERM), pharmacy (Pr. Géraldine Piel, LTBP – CIRM) and biology (Dr. Denis Mottet, MAGE Lab – GIGA Institute) have led a multidisciplinary research project called LIPEGALT funded in 2019 by the University of Liège's Actions de Recherche Concertée (ARC).
The results of this research have led to the publication of scientific articles in relevant scientific journals such as Journal of Controlled Release (JCR) and Advanced Healthcare Materials. The journal Advanced Healthcare Materials has highlighted this research by illustrating it on the Cover of their latest periodical (illustration ©Adeline Deward - Illumine - www.illuminescience.be).
The originality and innovation of this work, and in particular the synthesis and use of polymers of the Poly(N-methyl-N-vinylacetamide) type, has led to a patent being filed with the European Patent Office.
Another nice example of the fruitful interdisciplinary collaboration between ULiège's various research centers!
References
Poly(vinyl pyrrolidone) derivatives as PEG alternatives for stealth, non-toxic and less immunogenic siRNA-containing lipoplex delivery.
J Control Release. 2023 Sep;361:87-101. doi: 10.1016/j.jconrel.2023.07.031. Epub 2023 Aug 2. PMID: 37482343
