Design and development of a nanoemulsion system containing extract of Clinacanthus nutans (L.) leaves for transdermal delivery system by D-optimal mixture design and evaluation of its physicochemical properties

Clinacanthus nutans Lindau (C. nutans) is a well-known medicinal plant in South-East Asia that recently has attracted attention for its therapeutic characteristics and cosmeceutical applications. However, delivering the beneficial attributes of the bioactive ingredients into formulation is challenging due to poor solubility and low bioavailability of bioactive substances, which may hinder their effective transdermal delivery. Therefore, nanoemulsion has been chosen to be a carrier in encapsulation of bioactive ingredients C. nutans extract for pharmaceutical and cosmeceutical formulations. In this work, a D-optimal mixture design was used to determine the optimal composition of nanoemulsion-based system loaded with C. nutans leaves extract. The ultimate goal of the present work was to determine the optimum level of five independent variables (surfactant, oil, xanthan gum, bioactive extract, and water) in the optimal C. nutans nanoemulsion composition with minimum average droplet size. Under the optimal conditions, the predicted average droplet size was 99.99 nm. The actual response showed that the model was in good agreement with the predicted value with residual standard error (RSE) of 2.61%. The optimal nanoemulsion composition was observed to be stable under an accelerated stability study during storage at 25 and 45 ˚C for 90 days, centrifugal force and freeze–thaw cycles. Physicochemical characterizations of the optimal nanoemulsion showed its suitability for transdermal application due to its stability against phase separation

Predicting the optimum compositions of a transdermal nanoemulsion system containing an extract of Clinacanthus nutans leaves (L.) for skin antiaging by artificial neural network model

A nanoemulsion-based formulation containing leaf extracts of Clinacanthus nutans Lindau (C. nutans) was prepared for therapeutic use and optimized by artificial neural network (ANN). The model was applied to optimize the particle size of the transdermal nanoemulsion system containing an extract of C. nutans leaves for skin antiaging. Five universal learning algorithms—incremental back propagation, batch back propagation, quick propagation, genetic algorithm, and Levenberg-Marquardt—were used in the ANN to achieve the optimum topologies. The optimum topologies were selected among the learning algorithms trained with lowest root mean square values. Genetic Algorithm-5-13-1 was found to be the optimum topology for the final model to predict the optimum particle size. Under these conditions, the actual particle size of the optimum nanoemulsion compared well with the predicted values with the residual standard error of less than 1.5%. The final formulation was observed to be stable against phase separation under an accelerated stability study and during storage at room temperature and 45°C for 90 days. The dermal irritation assay demonstrated that the developed nanoemulsion was found to be compatible with human skin and could be classified as nonirritant. In vivo ultrasound attributes of the skin study showed that the collagen content increased significantly with the application of the C. nutans nanoemulsion among all 21 volunteers during the 21 days of the treatment period. Hence, ANN was found to be an effective tool for optimizing the nanoemulsion containing C. nutans leaves extract with efficacy to protect collagen from breakdown

Design and optimization of nanoemulsion formulation containing Clinacanthus nutans Lindau leaf extract for cosmeceutical application

Plant-based cosmetics have gained more attention compared to chemical-based product in the cosmetic industry due to its safety and efficacy. However, the primary challenges are incorporation of plant based extract in the formulation owing to its hydrophobicity, instability against oxidation and also difficulties in formulating a stable carrier system. Palm kernel oil esters (PKOEs) with great skin-penetrating abilities were selected to be blended with non-ionic surfactants in the formulation process. The structure of this nanoemulsion is defined as dispersions of self-assembled PKOEs and surfactants molecules in water resulting from solubilization of surfactant micelles. A newly developed nanoemulsion system was designed to incorporate of Clinacanthus nutans (C. nutans) leaves extract for transdermal application. C. nutans or also known as Belalai Gajah is a well-known medicinal plant in tropical Asian countries that has recently attracted attention for its therapeutic characteristics. Numerous reports have documented the biological activity of C. nutans, including its anti-inflammatory, anti-viral, antioxidant and anti-cancer properties. Extract of C. nutans have been well explored for their potential as pharmaceutical agents. However, work on its use in cosmeceutical application is unknown. Formulating nanoemulsion containing C. nutans extract has much promise as an effective delivery system and leads to the potential use of this plant extract in cosmeceutical application. Preparation of C. nutans leaves extract were obtained via sequential extraction and the optimization of the extraction process were carried out using Response Surface Methodology (RSM). The optimal condition suggested by the RSM model were extraction temperature of 60 °C, at 120 min with solvent ratio (water: ethanol) of 90: 10 v/v% which yielded 23.51% of extract. However, the insolubility of this extract in the methanol testing system has limited their accessibility to antioxidant assay. Thus, in this study extracts from sequential extraction with better solubility in testing system were chosen for further used. The properties of the extract showed their suitability to be used as source of antioxidants and exhibited non-toxicity against fibroblasts cells (3T3) which established their safe properties. Design of nanoemulsions system containing C. nutans extract involved several steps including screening of the level of variables, determination of the extract solubility and finally preparation of the nanoemulsions system. Under centrifugal force, all mixture of PKOEs: guava seed oil (GSO) in ratios of 9:1, 8:2 and 7:3 containing the extract did not show any precipitation at the bottom of the test tube. The ratio of 9:1 (PKOEs: GSO) was chosen as the suitable amount of oil mixture to be used in the formulation. The effect of composition on nanoemulsions; oil and surfactant on variation of particle size was investigated using Mixture Experimental Design (MED) and Artificial Neural Network (ANN). The nanoemulsion compositions predicted by different optimization methods were different. MED (labelled as CN1) suggested an optimal formulation containing 8.13% surfactant, 5.00% oil, 1.00% xanthan gum, 0.10% bioactive extract, 0.80% preservative, and 84.97% water to produce particles with a size of 97.38 nm. Meanwhile, ANN (labelled as CN2) suggested an optimal formulation containing 10.32% surfactant, 8.00% oil, 1.00% xanthan gum, 0.10% bioactive extract, 0.80% preservative, and 79.78% water to produce particles with a size of 125.40 nm. Although the particle size obtained by MED optimization was smaller than ANN, the residual standard error (RSE) for ANN was lower than MED which were 1.17% and 2.61%, respectively. This suggested that predicted and actual values of ANN had good correlation, implying that in this work ANN approach was an effective quantitative tool to be used in optimizing formulation design. Physicochemical characterization and stability evaluation were conducted for both formulations. Based on the results, both formulations showed their suitability for transdermal applications. These formulations were found out to be in nano sized with good stability against phase separation. The formulations were also stable under storage temperature of 25 °C and 45 °C for 90 days, freeze thaw cycles and centrifugal force tests. No distinct changes were observed in the particle size of the ANN formulation, indicating that the nanoemulsion prepared was stable at the chosen optimum composition. However, the particle size of the MED formulation was slightly increased in size over the storage period, nevertheless it was still in the nano-sized range (less than 200 nm). Transmission Electron Microscopy (TEM) images for both formulations showed the spherical shape of the oil droplets in the colloidal system and the encapsulation of the bioactive extract in the oil droplets. The optimal nanoemulsion had a shear-thinning behavior in both rheological experiments (steady state and oscillatory). This direct interaction fitted the Power Law Model indicating the pseudoplastic behavior in the system and gel structure existence which was one of the criteria in the formulation of transdermally applied cosmetics. Both formulations had pH values within the human skin range which was good for transdermal use. Taking into account the physicochemical characterization of both optimal nanoemulsions, ANN formulation labeled as CN2 was chosen to be the optimal composition in designing the C. nutans nanoemulsion. CN2 exhibited non-irritant property with a Human Irritancy Equivalent score of 0.13. In vivo ultrasound attributes of the skin study for CN2 showed that the collagen content increased significantly with the application of the C.nutans nanoemulsion among all 21 volunteers during the 21 d of the treatment period. The biophysical attributes of skinstudies demonstrated that skin hydration increased without any increment in transepidermal water loss. Thus, a stable C. nutans nanoemulsion was successfully developed which had the ability to promote collagen production in human skin and improved the skin barrier function and hence could be potentially used as a system for the delivery of natural antioxidant in cosmetic products

Murdannia loriformis: a review of ethnomedicinal uses, phytochemistry, pharmacology, contemporary application, and toxicology

This review provides an updated and comprehensive overview on the ethnomedicinal use, phytochemistry, pharmacology, and toxicology of M. loriformis. Phytochemical analysis of M. loriformis revealed that it is composed of phenolics, flavonoids, condensed tannins, chlorophylls, alkaloids, and steroids. Numerous compounds including syringic acid, ß-O-D glucopyranosyl-2-(2′-hydroxy-Z-6′-enecosamide) sphingosine, isovitexin, and 3β-O-D-glucopyranosyl-24ξ-ethylcholest-5-ene have been identified and isolated from this plant species. The present review attempts to bridge the gap between traditional use and pharmacological studies of M. loriformis while improving their existing therapeutic agents and product applications based on this plant

Monitoring soil resilience via the dynamic changes of selected physicochemical properties of soil in a tropical rehabilitated forest

Recovery of soil organic matter and mineral nutrient cycling are critical to the success of rehabilitation process of replanted forest. We investigated the dynamic changes in soil of selected physicochemical properties including organic carbon (C), nitrogen (N), phosphorus (P) and sulphur (S) of replanted forest rehabilitation that had been previously disturbed by anthropogenic activities. Soil samples were collected from the rehabilitated forest of three ages stands (3-, 12- and 23-years old) while samples from adjacent secondary forest was collected for comparison. Altogether, 36 samples were taken randomly with a soil auger at depths of 0-20 cm from a plot of 20 × 20 m2 at each site. Soils were analyzed for pH, bulk density, C, N, P and S. The data obtained were statistically analyzed using ANOVA with Tukey’s test performed by SAS 9.2 at P ≤ 0.05. Results showed that total C, N, P, C/N ratio and C/S ratio increased with age of rehabilitated forest except for pH, S and C/P ratio. Forest rehabilitation by planting indigenous tree species has shown a potential of recovery, but further investigation into the process control of the dynamic changes of soil physicochemical properties, particularly in the event of further ecosystem disturbance is needed

Effects of temperature, time, and solvent ratio on the extraction of phenolic compounds and the anti-radical activity of Clinacanthus nutans Lindau leaves by response surface methodology

Abstract Background Clinacanthus nutans Lindau is a well-known plant, native to tropical Asian countries. Reports on this plant that is rich in phenolic compounds have focused on its therapeutic anti-inflammatory, anti-herpes simplex, antioxidant, and anti-cancer characteristics. In this paper, the influence of the extraction parameters—temperatures (60–80 °C), times (80–120 min), and solvent ratios (70:30–90:10) of water:ethanol were investigated using response surface methodology in order to determine the optimum extraction conditions that could produce maximum extraction yields of the phenolic compounds and the highest anti-radical activity of the C. nutans extract. Results The optimum conditions suggested by the predicted model were: an extraction temperature of 60 °C, an extraction time of 120 min and a water:ethanol solvent ratio of 90:10 v/v%. The residual standard error of 0.2% indicated that there was no significant difference between the actual and predicted values and it proved that the models were adequate to predict the relevant responses. All the independent variables had a significant effect (p < 0.05) on all the responses which indicated that all extraction parameters employed in this study were important in the optimization process. The R2 values for three responses, extraction yields, DPPH radical scavenging activity and TPC were 0.9999, 0.9999 and 0.9983 respectively, suggesting that the quadratic polynomial models developed were satisfactorily accurate to be used in analyzing the interactions of the parameters (response and independent variables). Conclusion This study could be useful in the development of cosmeceutical products containing extracts of C. nutans