Lecithin-based nano-formulation of a standardised Andrographis paniculata (Burm.) Nees. aqueous extract in improving pharmacokinetics profile, stability, and antiasthma efficacy

Asthma, a chronic inflammatory airway disease, affects over 262 million people globally and is characterised by bronchial hyperresponsiveness with variable and recurring symptoms. The limited therapeutic options for asthma prophylaxis underscores the need for new preventive treatments. Andrographis paniculata aqueous extract (APAE) has shown promising anti-inflammatory and prophylactic effects against asthma in mouse models. The main bioactive compounds in APAE — andrographolide (AGP), neoandrographolide (NAG), and 14-deoxy-11,12- didehydroandrographolide (DDAG)—have demonstrated potent anti-inflammatory and antiasthmatic properties. However, their poor absorption and oral bioavailability limit their efficacy. Soy lecithin is a widely used food-grade emulsifier, used in various formulation due to its amphiphilic nature, stability, and ability to form nanosized particles with good encapsulation efficiency. These properties make soy-lecithin ideal for enhancing the bioavailability and shelf-life of bioactive compounds. This study aims to develop a lecithin-based nanoformulation of APAE (FAPAE) to improve oral absorption and enhance its antiasthma efficacy in a mouse asthma model. The optimised formulation (1:3) of the extract-to-lecithin ratio has an average vesicular size of 108.60±7.91, with polydispersity index (PDI) of 0.25±0.01, and zeta potentials of -48.90±4.51 mV respectively. For the rest of the study, the optimised formulation with the ratio of 1:3 with encapsulation efficiency of 68.15%, 75.00%, and 71.96% for AGP, NAG, and DDAG, respectively. FAPAE significantly prolonged the estimated shelf-life from 6.7 to 13.49 months for AGP and 7.72 to 9.74 months for NAG at 40°C/75% RH after 6 months. At 30°C/75% RH, FAPAE improved the shelf-life from 13.44 to 20.75 months for AGP and 13.05 to 21.74 months for NAG. The in vivo pharmacokinetics study of FAPAE revealed an increase in the AUC0-180 min from 66.99 to 102.91, 293.94 to 356.68, and 123.98 to 161.81 for AGP, NAG, and DDAG, respectively, in comparison to APAE. The peak plasma concentration increased from 0.81 to 1.28 μM for AGP, 3.00 to 3.85 μM for NAG, and 1.47 to 2.19 μM for DDAG. Subsequently, the antiasthmatic effects of FAPAE and APAE were evaluated in a House Dust Mite-induced asthma in Balb/c mice. Prophylactic treatment significantly ameliorated asthma symptoms such as lymphocyte cell infiltration, mucus hypersecretion, and airway resistance. FAPAE significantly (p<0.05) demonstrated a superior reduction in the expression of nuclear factor kappa-light-chain-enhancer of activated B cells protein and mucus-secreting gene. Histological evaluation of lung tissue samples of FAPAE compared to APAE treated groups showed a significant (p<0.05) reduction in peribronchial cell infiltration in the bronchial microenvironment, decrease in mucus secretion, and collagen deposition at a dose of 200 mg/kg. The findings of this study strongly suggest that the lecithin-based formulation may be a suitable carrier for APAE, enhancing oral bioavailability, stability, and efficacy. Consequently, utilising this carrier for the formulation of APAE holds promise as a drug delivery method for the prophylactic application of APAE in asthma. Finally, conducting a clinical trial is highly recommended. This will provide valuable insights into the formulation viability as a prophylactic intervention in humans.

Text FPSK(p) 2024 38 - Declaration Form.pdf Restricted to Repository staff only Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (935kB) Text FPSK(p) 2024 38 - Full Text.pdf Restricted to Repository staff only Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (51MB) Text FPSK(p) 2024 38.pdf Restricted to Repository staff only Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (52MB)

Actions (login required)

View Item