Formulation of andrographis paniculata-loaded nanoemulgel and its in vivo wound healing activity in mice

Abstract

Andrographis paniculata has been reported to contain several bioactive compounds proven to aid in wound healing mechanisms such as anti-inflammatory, anti-oxidant, analgesic, and anti-bacterial activities. However, there is no scientific study conducted to formulate this herb in the form of nanoemulgel for wound treatment. Hence, the objectives of this study were to optimise, characterise and evaluate a wound healing nanoemulgel containing A. paniculata extract for topical wound treatment application. In this study, virgin coconut oil nanoemulsion (VCO-NE) was optimised using quality by design (QbD) tools such as risk assessment and design of experiments (DoE) to choose the best formulation and processing parameters. The rheology and pharmacology studies were conducted for the prepared formulations. The in vivo wound healing assay was then conducted to evaluate the efficiency of the prepared formulations in mice. The QbD approach showed that the optimal VCO nanoemulsion could be formulated with Tween 20/Span 80 as surfactants, at hydrophilic-lipophilic balance (HLB) = 8, oil/surfactant = 2/1 and 85% water using a high-pressure homogeniser (HPH) at 800 bar for 5 cycles. The produced nanoemulsions had a droplet size of 151.5 ± 0.45 nm for blank VCO-NE, 141.17 ± 0.6 nm for S1 (1 mg/g A. paniculata extract) and 145.57 ± 0.74 for S2 (2 mg/g A. paniculata extract) as A. paniculata extract-loaded nanoemulsions (AP-NEs). Moreover, the developed nanoemulsions had a low polydispersity index (PDI) below 0.15 and relatively good stability with zeta potential -6.91 ± 0.64 for blank VCO-NE, -10.03 ± 1.36 for S1, and -16.40 ± 1.39 for S2. The prepared nanoemulsions were stable after 30 days when stored at 4 °C and 25 °C. Formulating nanoemulgel using the optimised nanoemulsions was found not to affect droplet size, PDI nor morphology. In addition, the rheology study showed that the prepared nanoemulgels could withstand segregation phenomena with preferred spreadability properties for long durations. Storage stability study also showed high stability for the nanoemulgels when stored at 4 °C and 25 °C for 90 days with no significant influence on the oil droplets size and PDI. Results from in vivo wound healing assay showed that, by day 11, wound treated with SG2 (1 mg/g A. paniculata extract-loaded nanoemulgel), which was developed from S2 nanoemulsion, exhibited 99.1% total wound recovery. The healing was found to be equivalent to 100% of the reference drug BETADINE®. In conclusion, results from this study indicated that nanoemulgel containing 1 mg/g A. paniculata extract could effectively promote wound healing process with less scar formation and no signs of irritation. Thus, A. paniculata extract nanoemulgel could be one of the potential ingredients for pharmaceutical and cosmeceutical applications, particularly for wound treatment.