The Therapeutic Potential of Novel Carnosine Formulations: Perspectives for Drug Development.
carnosine
conjugates
derivatives
drug delivery
drug development
nanoparticles
vesicular systems
Journal
Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453
Informations de publication
Date de publication:
23 May 2023
23 May 2023
Historique:
received:
11
04
2023
revised:
12
05
2023
accepted:
16
05
2023
medline:
28
6
2023
pubmed:
28
6
2023
entrez:
28
6
2023
Statut:
epublish
Résumé
Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide synthesized via the activity of the ATP-dependent enzyme carnosine synthetase 1 and can be found at a very high concentration in tissues with a high metabolic rate, including muscles (up to 20 mM) and brain (up to 5 mM). Because of its well-demonstrated multimodal pharmacodynamic profile, which includes anti-aggregant, antioxidant, and anti-inflammatory activities, as well as its ability to modulate the energy metabolism status in immune cells, this dipeptide has been investigated in numerous experimental models of diseases, including Alzheimer's disease, and at a clinical level. The main limit for the therapeutic use of carnosine is related to its rapid hydrolysis exerted by carnosinases, especially at the plasma level, reason why the development of new strategies, including the chemical modification of carnosine or its vehiculation into innovative drug delivery systems (DDS), aiming at increasing its bioavailability and/or at facilitating the site-specific transport to different tissues, is of utmost importance. In the present review, after a description of carnosine structure, biological activities, administration routes, and metabolism, we focused on different DDS, including vesicular systems and metallic nanoparticles, as well as on possible chemical derivatization strategies related to carnosine. In particular, a basic description of the DDS employed or the derivatization/conjugation applied to obtain carnosine formulations, followed by the possible mechanism of action, is given. To the best of our knowledge, this is the first review that includes all the new formulations of carnosine (DDS and derivatives), allowing a decrease or complete prevention of the hydrolysis of this dipeptide exerted by carnosinases, the simultaneous blood-brain barrier crossing, the maintenance or enhancement of carnosine biological activity, and the site-specific transport to different tissues, which then offers perspectives for the development of new drugs.
Identifiants
pubmed: 37375726
pii: ph16060778
doi: 10.3390/ph16060778
pmc: PMC10300694
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : PON REACT project (Azione IV.4-"Dottorati e contratti di ricerca su tematiche dell'innovazione", nuovo Asse IV del PON Ricerca e Innovazione 2014-2020 "Istruzione e ricer-ca per il recupero-REACT-EU"
ID : CUP E65F21002640005
Organisme : Ricerca di Ateneo 2020-2022, Piano di incentivi per la ricerca (PIA.CE.RI.), Linea di intervento 2; Naso, Nanomedicina e Neuroterapie: Le 3 N per il target cerebrale di molecole bioattive (3 N-ORACLE), progetto interdipartimentale
ID : CUP 57722172124
Organisme : Italian Ministry of Health Research Program
ID : RC2022-24
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