Chitosan-Coated Liposomes for Intranasal Delivery of Ghrelin: Enhancing Bioavailability to the Central Nervous System

Background/Objectives: Cachexia is a syndrome characterized by the progressive loss of muscle mass, leading to high morbidity and mortality. Ghrelin (Ghrl) exhibits orexigenic, anabolic, and anti-inflammatory properties with therapeutic potential. However, its low bioavailability limits the efficacy of systemic treatments. This study aimed to develop chitosan-coated liposomes containing Ghrl (CH-Lip + Ghrl) for intranasal administration, allowing quantification of Ghrl brain bioavailability using a system optimized for a labile neuropeptide. Methods: The formulation was prepared using thin-film hydration, followed by extrusion and chitosan coating. It was characterized based on morphology, size, zeta potential, stability, encapsulation efficiency, and cell viability. Permeation and mucoadhesion were evaluated ex vivo using porcine nasal mucosa, and cerebral bioavailability was assessed in Wistar rats. Results: CH-Lip + Ghrl had an average of 152.4 ± 0.2 nm (evaluated by DLS), a polydispersity index of 0.159 ± 0.018, a zeta potential of +60.8 ± 6.6 mV, and an encapsulation efficiency of 53.2 ± 0.8%, maintaining stability for 180 days. At 1% (v/v) in culture medium, the formulation retained 73.2 ± 8.4% of the viability in nasal epithelial cells and 81.9 ± 4.8% in neuroblastoma cells. Chitosan coating increased ex vivo mucoadhesion 1.7-fold and permeation 1.3-fold. In vivo, 25 min after intranasal administration, CH-Lip + Ghrl delivered 48.2 ± 8.8% of the dose to the brain, whereas free Ghrl was undetectable. Conclusions: The intranasal administration of CH-Lip + Ghrl enhances cerebral bioavailability of Ghrl. This study integrates a chemically labile neuropeptide with chitosan-coated liposomes for direct brain delivery, representing an innovative platform for future translational studies.