A Review on the Delivery of Plant-Based Antidiabetic Agents Using Nanocarriers: Current Status and Their Role in Combatting Hyperglycaemia.

Diabetes mellitus is a prevalent metabolic syndrome that is associated with high blood glucose levels. The number of diabetic patients is increasing every year and the total number of cases is expected to reach more than 600 million worldwide by 2045. Modern antidiabetic drugs alleviate hyperglycaemia and complications that are caused by high blood glucose levels. However, due to the side effects of these drugs, plant extracts and bioactive compounds with antidiabetic properties have been gaining attention as alternative treatments for diabetes. Natural products are biocompatible, cheaper and expected to cause fewer side effects than the current antidiabetic drugs. In this review, various nanocarrier systems are discussed, such as liposomes, niosomes, polymeric nanoparticles, nanoemulsions, solid lipid nanoparticles and metallic nanoparticles. These systems have been applied to overcome the limitations of the current drugs and simultaneously improve the efficacy of plant-based antidiabetic drugs. The main challenges in the formulation of plant-based nanocarriers are the loading capacity of the plant extracts and the stability of the carriers. A brief review of lipid nanocarriers and the amphipathic properties of phospholipids and liposomes that encapsulate hydrophilic, hydrophobic and amphiphilic drugs is also described. A special emphasis is placed on metallic nanoparticles, with their advantages and associated complications being reported to highlight their effectiveness for treating hyperglycaemia. The present review could be an interesting paper for researchers who are working in the field of using plant extract-loaded nanoparticles as antidiabetic therapies.

Lipid-based nanoparticles for psoriasis treatment: a review on conventional treatments, recent works, and future prospects.

Psoriasis is a lingering inflammatory skin disease that attacks the immune system. The abnormal interactions between T cells, immune cells, and inflammatory cytokines causing the epidermal thickening. International guidelines have recommended topical treatments for mild to moderate psoriasis whilst systemic and phototherapy treatments for moderate to severe psoriasis. However, current therapeutic approaches have a wider extent to treat moderate to severe type of psoriasis especially since the emergence of diverse biologic agents. In the meantime, topical delivery of conventional treatments has prompted many unsatisfactory effects to penetrate through the skin (stratum corneum). By understanding the physiology of stratum corneum barrier functions, scientists have developed different types of lipid-based nanoparticles like solid lipid nanoparticles, nanostructured lipid carriers, nanovesicles, and nanoemulsions. These novel drug delivery systems help the poorly solubilised active pharmaceutical ingredient reaches the targeted site seamlessly because of the bioavailability feature of the nanosized molecules. Lipid-based nanoparticles for psoriasis treatments create a paradigm for topical drug delivery due to their lipids' amphiphilic feature to efficiently encapsulate both lipophilic and hydrophilic drugs. This review highlights different types of lipid-based nanoparticles and their recent works of nano formulated psoriasis treatments. The encapsulation of psoriasis drugs through lipid nanocarriers unfold numerous research opportunities in pharmaceutical applications but also draw challenges for the future development of nano drugs.

Extraction, anti-tyrosinase, and antioxidant activities of the collagen hydrolysate derived from Rhopilema hispidum.

The study was conducted to determine anti-tyrosinase and antioxidant activities of the extracted collagen hydrolysate (CH) derived from Malaysian jellyfish, Rhopilema hispidum. Collagen was extracted using 1:1 (w:v) 0.1 M NaOH solution at temperature 25 °C for 48 hr followed by treatment of 1:2 (w:v) distilled water for another 24 hr and freeze-dried. The extracted collagen was hydrolyzed using papain at optimum temperature, pH and enzyme/substrate ratio [E/S] of 60 °C, 7.0 and 1:50, respectively. CH was found to exhibit tyrosinase inhibitory activity, DPPH radical scavenging and metal ion-chelating assays up to 64, 28, and 83%, respectively, after 8 hr of hydrolysis process. The molecular weight of CH was found <10 kDa consisting of mainly Gly (19.219%), Glu (10.428%), and Arg (8.848%). The UV-visible spectrum analysis showed a major and minor peak at 218 and 276 nm, accordingly. The FTIR spectroscopy confirmed the amide groups in CH. The SEM images demonstrated spongy and porous structure of CH. In the cytotoxicity study, CH has no cytotoxicity against mouse embryonic 3T3 fibroblast cell line with IC50 value >500 µg/ml. Results revealed that the CH generated from this study has a potential to be developed as active ingredient in cosmeceutical application.

Optimization and Characterization of Palm Oil-based Nanoemulsion Loaded with Parthenium hysterophorus Crude Extract for Natural Herbicide Formulation.

The present study revealed the optimization of nanoemulsion containing palm oil derivatives and Parthenium hysterophorus L. crude extract (PHCE) as pre-emergence herbicide formulation against Diodia ocimifolia. The nanoemulsion formulation was prepared by high energy emulsification method, and it was optimized by mixture experimental design (MED). From the optimization process, analysis of variance (ANOVA) showed a fit quadratic polynomial model with an optimal formulation composition containing 30.91% of palm kernel oil ester (PKOE), 28.48% of mixed surfactants (Tensiofix and Tween 80, 8:2), 28.32% of water and 12.29% of PHCE. The reading of both experimental and predicted particle size in the verification experiment were acceptable with a residual standard error (RSE) was less than 2%. Under the optimal condition, the smallest particle size obtained was 140.10 nm, and the particle was shown by morphology analysis to be spherical and demonstrated good stability (no phase separation) under centrifugation and different storage conditions (25 ± 5°C and 45°C). Nanoemulsion stored for 60 days exhibits monodisperse emulsion with a slight increase of particle size. The increase in particle size over time might have contributed by Ostwald ripening phenomenon which is shown by a linear graph from Ostwald ripening rate analysis. In the in vitro germination test, P. hysterophorus nanoemulsion (PHNE) was shown to cause total inhibition of D. ocimifolia seed at lower concentration (5 g L-1) as compared to PHCE (10 g L-1). The finding of the research could potentially serve as a platform for the development of palm oil based formulation containing plant crude extract for green weed management.

Improvement of physicochemical properties of nanocolloidal carrier loaded with low water solubility drug for parenteral cancer treatment by Response Surface Methodology.

Nanoemulsions have been used as a drug carrier system, particularly for poorly water-soluble drugs. Sorafenib is a poorly soluble drug and also there is no parenteral treatment. The aim of this study is the development of nanoemulsions for intravenous administration of Sorafenib. The formulations were prepared by high energy emulsification method and optimized by using Response Surface Methodology (RSM). Here, the effect of independent composition variables of lecithin (1.16-2.84%, w/w), Medium-Chain Triglycerides (2.32-5.68%, w/w) and polysorbate 80 (0.58-1.42%, w/w) amounts on the properties of Sorafenib-loaded nanoemulsion was investigated. The three responses variables were particle size, zeta potential, and polydispersity index. Optimization of the conditions according to the three dependent variables was performed for the preparation of the Sorafenib-loaded nanoemulsions with the minimum value of particle size, suitable rage of zeta potential, and polydispersity index. A formulation containing 0.05% of Sorafenib kept its properties in a satisfactory range over the evaluated period. The composition with 3% Medium-Chain Triglycerides, 2.5% lecithin and 1.22% polysorbate 80 exhibited the smallest particle size and polydispersity index (43.17 nm and 0.22, respectively) with the zeta potential of -38.8 mV was the optimized composition. The fabricated nanoemulsion was characterized by the transmission electron microscope (TEM), viscosity, and stability assessment study. Also, the cytotoxicity result showed that the optimum formulations had no significant effect on a normal cell in a low concentration of the drug but could eliminate the cancer cells. The dose-dependent toxicity made it a suitable candidate for parenteral applications in the treatment of breast cancer. Furthermore, the optimized formulation indicated good storage stability for 3 months at different temperatures (4 ±â€¯2 °C, 25 ±â€¯2 °C and 45 ±â€¯2 °C).

Excipient selection and aerodynamic characterization of nebulized lipid-based nanoemulsion loaded with docetaxel for lung cancer treatment.

Docetaxel has demonstrated extraordinary anticancer effects on lung cancer. However, lack of optimal bioavailability due to poor solubility and high toxicity at its therapeutic dose has hampered the clinical use of this anticancer drug. Development of nanoemulsion formulation along with biocompatible excipients aimed for pulmonary delivery is a potential strategy to deliver this poorly aqueous soluble drug with improved bioavailability and biocompatibility. In this work, screening and selection of pharmaceutically acceptable excipients at their minimal optimal concentration have been conducted. The selected nanoemulsion formulations were prepared using high-energy emulsification technique and subjected to physicochemical and aerodynamic characterizations. The formulated nanoemulsion had mean particle size and ζ-potential in the range of 90 to 110 nm and - 30 to - 40 mV respectively, indicating high colloidal stability. The pH, osmolality, and viscosity of the systems met the ideal requirement for pulmonary application. The DNE4 formulation exhibited slow drug release and excellent stability even under the influence of extreme environmental conditions. This was further confirmed by transmission electron microscopy as uniform spherical droplets in nanometer range were observed after storage at 45 ± 1 °C for 3 months indicating high thermal stability. The nebulized DNE4 exhibited desirable aerosolization properties for pulmonary delivery application and found to be more selective on human lung carcinoma cell (A549) than normal cell (MRC-5). Hence, these characteristics make the formulation a great candidate for the potential use as a carrier system for docetaxel in targeting lung cancer via pulmonary delivery.

Development of a kojic monooleate-enriched oil-in-water nanoemulsion as a potential carrier for hyperpigmentation treatment.

INTRODUCTION: Kojic monooleate (KMO) is an ester derived from a fungal metabolite of kojic acid with monounsaturated fatty acid, oleic acid, which contains tyrosinase inhibitor to treat skin disorders such as hyperpigmentation. In this study, KMO was formulated in an oil-in-water nanoemulsion as a carrier for better penetration into the skin. METHODS: The nanoemulsion was prepared by using high and low energy emulsification technique. D-optimal mixture experimental design was generated as a tool for optimizing the composition of nanoemulsions suitable for topical delivery systems. Effects of formulation variables including KMO (2.0%-10.0% w/w), mixture of castor oil (CO):lemon essential oil (LO; 9:1) (1.0%-5.0% w/w), Tween 80 (1.0%-4.0% w/w), xanthan gum (0.5%-1.5% w/w), and deionized water (78.8%-94.8% w/w), on droplet size as a response were determined. RESULTS: Analysis of variance showed that the fitness of the quadratic polynomial fits the experimental data with F-value (2,479.87), a low P-value (P<0.0001), and a nonsignificant lack of fit. The optimized formulation of KMO-enriched nanoemulsion with desirable criteria was KMO (10.0% w/w), Tween 80 (3.19% w/w), CO:LO (3.74% w/w), xanthan gum (0.70% w/w), and deionized water (81.68% w/w). This optimum formulation showed good agreement between the actual droplet size (110.01 nm) and the predicted droplet size (111.73 nm) with a residual standard error <2.0%. The optimized formulation with pH values (6.28) showed high conductivity (1,492.00 µScm-1) and remained stable under accelerated stability study during storage at 4°C, 25°C, and 45°C for 90 days, centrifugal force as well as freeze-thaw cycles. Rheology measurement justified that the optimized formulation was more elastic (shear thinning and pseudo-plastic properties) rather than demonstrating viscous characteristics. In vitro cytotoxicity of the optimized KMO formulation and KMO oil showed that IC50 (50% inhibition of cell viability) value was >100 µg/mL. CONCLUSION: The survival rate of 3T3 cell on KMO formulation (54.76%) was found to be higher compared to KMO oil (53.37%) without any toxicity sign. This proved that the KMO formulation was less toxic and can be applied for cosmeceutical applications.

Optimization of Quercetin loaded Palm Oil Ester Based Nanoemulsion Formulation for Pulmonary Delivery.

In this research, the palm oil ester (POE)- based nanoemulsion formulation containing quercetin for pulmonary delivery was developed. The nanoemulsion formulation was prepared by high energy emulsification method and then further optimized using D-optimal mixture design. The concentration effects of the mixture of POE:ricinoleic acid (RC), ratio 1:1 (1.50-4.50 wt.%), lecithin (1.50-2.50 wt.%), Tween 80 (0.50-1.00 wt.%), glycerol (1.50-3.00 wt.%), and water (88.0-94.9 wt.%) towards the droplet size were investigated. The results showed that the optimum formulation with 1.50 wt.% POE:RC, 1.50 wt.% lecithin, 1.50 wt.% Tween 80, 1.50 wt.% glycerol and 93.90 % water was obtained. The droplet size, polydispersity index (PDI) and zeta potential of the optimized formulation were 110.3 nm, 0.290 and －37.7 mV, respectively. The formulation also exhibited good stability against storage at 4℃ for 90 days. In vitro aerosols delivery evaluation showed that the aerosols output, aerosols rate and median mass aerodynamic diameter of the optimized nanoemulsion were 99.31%, 0.19 g/min and 4.25 µm, respectively. The characterization of physical properties and efficiency for aerosols delivery results suggest that POE- based nanoemulsion containing quercetin has the potential to be used for pulmonary delivery specifically for lung cancer treatment.

Enhancement of physicochemical properties of nanocolloidal carrier loaded with cyclosporine for topical treatment of psoriasis: in vitro diffusion and in vivo hydrating action.

Psoriasis is a chronic autoimmune disease that cannot be cured. It can however be controlled by various forms of treatment, including topical, systemic agents, and phototherapy. Topical treatment is the first-line treatment and favored by most physicians, as this form of therapy has more patient compliance. Introducing a nanoemulsion for transporting cyclosporine as an anti-inflammatory drug to an itchy site of skin disease would enhance the effectiveness of topical treatment for psoriasis. The addition of nutmeg and virgin coconut-oil mixture, with their unique properties, could improve cyclosporine loading and solubility. A high-shear homogenizer was used in formulating a cyclosporine-loaded nanoemulsion. A D-optimal mixture experimental design was used in the optimization of nanoemulsion compositions, in order to understand the relationships behind the effect of independent variables (oil, surfactant, xanthan gum, and water content) on physicochemical response (particle size and polydispersity index) and rheological response (viscosity and k-value). Investigation of these variables suggests two optimized formulations with specific oil (15% and 20%), surfactant (15%), xanthan gum (0.75%), and water content (67.55% and 62.55%), which possessed intended responses and good stability against separation over 3 months' storage at different temperatures. Optimized nanoemulsions of pH 4.5 were further studied with all types of stability analysis: physical stability, coalescence-rate analysis, Ostwald ripening, and freeze-thaw cycles. In vitro release proved the efficacy of nanosize emulsions in carrying cyclosporine across rat skin and a synthetic membrane that best fit the Korsmeyer-Peppas kinetic model. In vivo skin analysis towards healthy volunteers showed a significant improvement in the stratum corneum in skin hydration.

Modification of palm kernel oil esters nanoemulsions with hydrocolloid gum for enhanced topical delivery of ibuprofen.

INTRODUCTION: During recent years, there has been growing interest in the use of nanoemulsion as a drug-carrier system for topical delivery. A nanoemulsion is a transparent mixture of oil, surfactant and water with a very low viscosity, usually the product of its high water content. The present study investigated the modification of nanoemulsions with different hydrocolloid gums, to enhanced drug delivery of ibuprofen. The in vitro characterization of the initial and modified nanoemulsions was also studied. METHODS: A palm kernel oil esters nanoemulsion was modified with different hydrocolloid gums for the topical delivery of ibuprofen. Three different hydrocolloids (gellan gum, xanthan gum, and carrageenan) were selected for use. Ternary phase diagrams were constructed using palm kernel oil esters as the oil, Tween 80 as the surfactant, and water. Nanoemulsions were prepared by phase inversion composition, and were gradually mixed with the freshly prepared hydrocolloids. The initial nanoemulsion and modified nanoemulsions were characterized. The abilities of the nanoemulsions to deliver ibuprofen were assessed in vitro, using a Franz diffusion cell fitted with rat skin. RESULTS: No significant changes were observed in droplet size (~16-20 nm) but a significant difference in polydispersity indexes were observed before and after the modification of nanoemulsions using gellan gum, carrageenan, and xanthan gum. The zeta potentials of the initial nanoemulsions (-11.0 mV) increased to -19.6 mV, -13.9 mV, and -41.9 mV, respectively. The abilities of both the initial nanoemulsion (T802) and the modified nanoemulsion to deliver ibuprofen through the skin were evaluated in vitro, using Franz diffusion cells fitted with rat skin. The in vitro permeation data showed that the modified nanoemulsion (Kp value of 55.4 × 10(-3) cm · h(-1)) increased the permeability of ibuprofen 4.40 times over T802 (Kp value of 12.6 × 10(-3) cm · h(-1)) (P < 0.05). CONCLUSION: The modified nanoemulsion may be a promising vehicle to enhance the permeation of ibuprofen for topical delivery.