Cachexia: pathophysiology and ghrelin liposomes for nose-to-brain delivery

Cachexia, a severe multifactorial condition that is underestimated and unrecognized in patients, is characterized by continuous muscle mass loss that leads to progressive functional impairment, while nutritional support cannot completely reverse this clinical condition. There is a strong need for more effective and targeted therapies for cachexia patients. There is a need for drugs that act on cachexia as a distinct and treatable condition to prevent or reverse excess catabolism and inflammation. Due to ghrelin properties, it has been studied in the cachexia and other treatments in a growing number of works. However, in the body, exogenous ghrelin is subject to very rapid degradation. In this context, the intranasal release of ghrelin-loaded liposomes to cross the blood-brain barrier and the release of the drug into the central nervous system may be a promising alternative to improve its bioavailability. The administration of nose-to-brain liposomes for the management of cachexia was addressed only in a limited number of published works. This review focuses on the discussion of the pathophysiology of cachexia, synthesis and physiological effects of ghrelin and the potential treatment of the diseased using ghrelin-loaded liposomes through the nose-to-brain route. Funded by PROSUP/Coordination of Superior Level Staff Improvement (CAPES), University of Sorocaba (UNISO), São Paulo Research Foundation (FAPESP/2014/50928-2), Brazil, granted to MVC, and by the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE), co-financed by FEDER, under the Partnership Agreement PT2020 granted to EBS (UIDB/04469/2020 (strategic fund)