Title : Preparation and characterization of inhaled luteolin nano-liposomes for the potential management of pulmonary arterial hypertension
Abstract:
Luteolin is a natural flavonoid abundant in several fruits, vegetables, and medicinal herbs. Although luteolin has numerous pharmacological activities, its low water solubility and bioavailability restrict its therapeutic efficacy. This work aims to overcome these limitations by developing an inhalable luteolin-loaded nanoliposome and investigating its anti-pulmonary arterial hypertension effects. The thin-film rehydration method was applied to formulate the inhalable luteolin liposomes using two phospholipids with high-phase transition temperatures and cholesterol without surfactant. The aerodynamic behaviour of the developed luteolin nano-formulation was determined using the next-generation impactor, and its effects on the TGF-β pathway and anti-proliferative effects were determined using cell-based assays. The novel formulated inhalable luteolin liposomes had an average liposome size of 117 ± 7.4 nm, a polydispersity index of 0.1, a zeta potential of −26.7 ± 3 mV, and high encapsulation efficiency. The newly formulated luteolin nano-liposome exhibited excellent aerodynamic properties as follows: the mass median aerodynamic diameter was 3.91 ± 0.04 µm, the fine particle fraction ≤ 5 µm was 58.59 ± 0.34%, and the percentage of particles ≤ 3 µm was 38.84 ± 0.28%. This indicates that the newly developed luteolin liposome possesses all the necessary characteristics for inhalation and is anticipated to be effectively delivered deeply into the lungs. The in vitro release study revealed a significantly enhanced luteolin release profile using nano-liposomes compared with free luteolin (p ≤ 0.001). The TGF-β pathway is stimulated in individuals with pulmonary arterial hypertension lungs. The free luteolin and nano-liposomes encapsulated luteolin significantly inhibit the TGF-β/ SMAD 3 dependent signalling in a dose-dependent manner using a TGFβ-responsive reporter assay (p ≤ 0.001). Interestingly, the MTT assay results showed that the developed luteolin nano-liposomes have a markedly higher anti-proliferative effect than free luteolin on mutant mouse pulmonary arterial smooth muscle cells (p ≤ 0.001). These findings indicate that the newly formulated luteolin nano-liposome could be used in experimental research and clinical settings for pulmonary arterial hypertension.
Audience Will Take Away Notes:
- This presentation will provide a practical example of how nano-liposome formulation improves the in vitro effects of low-water-soluble natural compounds compared with delivering free compounds
- It will help the audiences to understand the factors that help maintain the stability of inhalable liposomes during nebulisation
- It will offer a successful example of formulating high-safety profile inhalable nano-liposomes for natural compounds without needing any surfactant or co-surfactant
- The newly developed luteolin nano-liposome inhibits TGFβ signalling and has anti-proliferative effects in cell-based studies and thus holds promise as a potential treatment for pulmonary arterial hypertension
