The therapeutic use of peptides has increasingly recognized in the development of new therapies. However, the susceptible enzymatic cleavage is a barrier that needs to overcome. Nose-to-brain delivery associated with liposomes can protect peptides against biodegradation and improve the accessibility to brain targets. The aim was to develop a liposomal formulation as ghrelin carrier. The quality by design (QbD) approach was used as a strategy for method development. The initial risk assessments were carried out using a fishbone diagram. A screening design study was performed for the critical material attributes/critical process parameters (CMAs/CPPs) on critical quality attributes (CQAs). Liposomes were obtained by hydrating phospholipid films, followed by extrusion or homogenization, and coated with chitosan. The optimized liposome formulation was produced by high-pressure homogenization coated with chitosan, and the resulted were liposomes size 72.25 ± 1.46 nm, PDI of 0.300 ± 0.027, the zeta potential of 50.3 ± 1.46 mV, and encapsulation efficiency of 53.2%. Moreover, chitosan coating improved performance in ex vivo permeation and mucoadhesion analyzes when compared to the uncoated liposome. In this context, chitosan coating is essential for the performance of the formulations in the ex vivo permeation and mucoadhesion analyzes. The intranasal administration of ghrelin liposomes coated with chitosan offers an innovative opportunity to treat cachexia.

Objectives Nanotechnology-based nasal delivery systems have gained interest as a way of overcoming low drug bioavailability, limited brain exposure, fast metabolism and elimination, high doses, and unwanted side effects. The main benefits of intranasal administration include the non-invasive method, easy accessibility, porous epithelial barrier and highly vascularized tissue. However, it is imperative to identify interactions between the materials used and the nasal biological environment to ensure proper release. Methods Specific factors have been considered to comply with the strict nasal drug administration criteria. Given the broad interest in the nasal drug delivery system, this review summarizes ways to develop formulations for intranasal drug delivery and the main biopharmaceutical challenges. Key findings We have examined principal factors in nasal administration, such as physiological aspects of the nose, drug and biopharmaceutical properties, formulation properties, and nasal devices for drug delivery. Conclusions This review highlights new insights into different nanotechnology-based approaches for intranasal use and focuses on recent developments in topical nasal drug delivery systems (DDS), outlining the advantages and limitations of each system. The present article confines itself to research and novel concepts and the different strategies developed to increase bioavailability, safety, and a route to brain delivery.