Optimization of the development of Inhalable EGCG nano-Liposome as a Potential Treatment for Pulmonary Arterial Hypertension by Implementation of Design of Experiments Approach

Fatma Haddad¹, Khaled Assi¹, Talat Nasim¹, and Rajendran Gopalan¹

¹ School of Pharmacy and Medical Sciences, University of Bradford, Bradford, United Kingdom.

Summary

 Epigallocatechin gallate (EGCG), the main ingredient in green tea, holds promise as a potential treatment for pulmonary arterial hypertension (PAH). However, EGCG has many drawbacks including stability issues, low bioavailability, and short half-life. Therefore, research aimed to optimize the development of inhalable EGCG nano-liposome formulation to overcome EGCG drawbacks. Using the Design expert software version-13, the design of experiments (DOE) strategy was applied to study the impact of formulation compositions on the liposomal characteristics and to develop the optimum inhalable EGCG nano-liposome formulation. Then it was characterized, and its aerodynamic behavior was identified utilizing the next-generation impactor (NGI). The in vitro effect of the optimum EGCG nano-liposome was determined using the reporter assay. The prepared optimum inhalable EGCG liposome has the following experimental characteristics: the average liposome size of 105 nm, polydispersity index (PDI) of 0.18, the zeta potential of -25.5 mV, encapsulation efficiency of 90.5%, and the PDI after three months of 0.19. All the actual results of these responses were in great agreement with the anticipated values by the model. Its aerodynamic properties were as follows: the mass median aerodynamic diameter (MMAD) was 4.41 µm, and the fine particle fraction (FPF) (<5µm) was 53.46%. The stability study has shown that the liposomal formulation of EGCG was stable for at least three months with an excellent encapsulation efficiency of more than 90%. The optimum nano-liposome has also been shown to be stable after nebulization using the vibrating mesh nebulizer and has inhibited the reporter activity in a dose-dependent manner. 

Key Message

 An optimum inhalable EGCG nano-liposome formulation was formulated using the design of experiments strategy, characterized, and its aerodynamic behavior was studied. This inhalable EGCG nano-liposome has shown to be effective in in vitro inhibition of reporter assay as a potential treatment for PAH.