Development and Optimisation of Inhalable EGCG Nano-Liposomes as a Potential Treatment for Pulmonary Arterial Hypertension by Implementation of the Design of Experiments Approach

by Selleckchem | Mar 21 2023

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 a short half-life. Therefore, the purpose of this research was to develop and optimize an inhalable EGCG nano-liposome formulation aiming to overcome EGCG's drawbacks by applying a design of experiments strategy. The aerodynamic behaviour of the optimum formulation was determined using the next-generation impactor (NGI), and its effects on the TGF-β pathway were determined using a cell-based reporter assay. The newly formulated inhalable EGCG liposome had an average liposome size of 105 nm, a polydispersity index (PDI) of 0.18, a zeta potential of -25.5 mV, an encapsulation efficiency of 90.5%, and a PDI after one month of 0.19. These results are in complete agreement with the predicted values of the model. Its aerodynamic properties were as follows: the mass median aerodynamic diameter (MMAD) was 4.41 µm, the fine particle fraction (FPF) was 53.46%, and the percentage of particles equal to or less than 3 µm was 34.3%. This demonstrates that the novel EGCG liposome has all the properties required to be inhalable, and it is expected to be deposited deeply in the lung. The TGFβ pathway is activated in PAH lungs, and the optimum EGCG nano-liposome inhibits TGFβ signalling in cell-based studies and thus holds promise as a potential treatment for PAH.

Comments：

The research aimed to develop an inhalable EGCG nano-liposome formulation to overcome the stability issues, low bioavailability, and short half-life of EGCG for treating pulmonary arterial hypertension (PAH). The design of experiments strategy was applied to optimize the formulation. The aerodynamic behavior of the optimum formulation was determined using the next-generation impactor (NGI), and its effects on the TGF-β pathway were determined using a cell-based reporter assay.

The results showed that the newly formulated inhalable EGCG liposome had an average liposome size of 105 nm, a PDI of 0.18, a zeta potential of -25.5 mV, an encapsulation efficiency of 90.5%, and a PDI after one month of 0.19. These results were consistent with the predicted values of the model. The aerodynamic properties of the formulation were also promising, with an MMAD of 4.41 µm, an FPF of 53.46%, and a percentage of particles equal to or less than 3 µm of 34.3%. These characteristics suggest that the novel EGCG liposome has all the properties required to be inhalable and deposited deeply in the lung.

The TGFβ pathway is activated in PAH lungs, and the optimum EGCG nano-liposome was shown to inhibit TGFβ signaling in cell-based studies. This finding indicates that the novel EGCG liposome has the potential to be an effective treatment for PAH.

In summary, the research successfully developed an inhalable EGCG nano-liposome formulation with desirable properties and demonstrated its potential effectiveness in treating PAH by inhibiting the TGFβ pathway. The results of this study could pave the way for further research and development of EGCG-based therapies for PAH.