Author(s): Barros, Cecília de ; Aranha, Norberto ; Severino, Patrícia ; Souto, Eliana B. ; Zielińska, Aleksandra ; Lopes, André ; Rios, Alessandra ; Batain, Fernando ; Crescencio, Kessi ; Chaud, Marco ; Alves, Thais
Date: 2021
Persistent ID: https://hdl.handle.net/10316/105332
Origin: Estudo Geral - Universidade de Coimbra
Subject(s): ghrelin; intranasal rout; liposomes; quality by design (QbD); cachexia; undernourishment; starvation
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.
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001; São Paulo Research Foundation (FAPESP-grant numbers # 2018-18364-2; #2018/10799-0; #2017/10789-1) and University of Sorocaba (UNISO), São Paulo, Brazil.
