Oil-in-water (o/w) emulsion is utilized as an insecticide delivery system for mosquito control. However, evaporation inhibition adjuvant is needed to prevent fog drift, inhibit release of insecticidal actives and prolong suspension time. In the current study, we evaluated the effect of different short-chain alcohols, namely, propylene glycol, 1,3-propanediol, glycerol and crude glycerol, as adjuvants on the physicochemical properties of d-phenothrin o/w emulsion system. The bioactivity of optimized formulations containing 20 wt% glycerol (D1), 20 wt% propylene glycol (D2) and without added alcohol (negative control) were tested against larvae, pupae and adult Aedes aegypti (Ae. aegypti). It was found that propylene glycol produced smaller droplets at lower concentrations but poor long-term stability at higher concentrations, whereas glycerol had an appreciable effect on initial droplet size and stability with increasing concentration. According to the dose-response bioassays and room size chamber testing, the highest larvicidal, pupicidal and adulticidal activities were observed with D2, followed by D1 and negative control. Overall, the above study demonstrated improved emulsion stabilities and potency against Ae. aegypti larvae, pupae and adults using glycerol as adjuvant for effective mosquito control.
Fungal infections of skin including mycoses are one of the most common infections in skin or skins. Mycosis is caused by dermatophytes, non-dermatophyte moulds and yeasts. Various studies show different drugs to treat mycoses, yet there is need to treat it with applied drugs delivery. This study was designed to prepare a bio curcumin (CMN) nanoemulsion (CMN-NEs) for transdermal administration to treat mycoses. The self-nanoemulsification approach was used to prepare a nanoemulsion (NE), utilizing an oil phase consisting of Cremophor EL 100 (Cre EL), glyceryl monooleate (GMO), and polyethylene glycol 5000 (PEG 5000). Particle size (PS), polydispersity index (PDI), zeta potential (ZP), Fourier transform infrared (FTIR) spectrophotometric analysis, and morphological analyses were performed to evaluate the nanoemulsion (NE). The in vitro permeation of CMN was investigated using a modified vertical diffusion cell with an activated dialysis membrane bag. Among all the formulations, a stable, spontaneously produced nanoemulsion was determined with 250 mg of CMN loaded with 10 g of the oil phase. The average droplet size, ZP, and PDI of CMN-NEs were 90.0 ± 2.1 nm, - 7.4 ± 0.4, and 0.171 ± 0.03 mV, respectively. The release kinetics of CMN differed from zero order with a Higuchi release profile as a result of nanoemulsification, which also significantly increased the flux of CMN permeating from the hydrophilic matrix gel. Overall, the prepared nanoemulsion system not only increased the permeability of CMN but also protected it against chemical deterioration. Both CMN-ME (24.0 ± 0.31 mm) and CMN-NE gel (29.6 ± 0.25 mm) had zones of inhibition against Candida albicans that were significantly larger than those of marketed Itrostred gel (21.5 ± 0.34 mm). The prepared CMN-NE improved the bioavailability, better skin penetration, and the CMN-NE gel enhanced the release of CMN from the gel matrix on mycotic patients.
Eucalyptus globulus is an aromatic medicinal plant which known for its 1,8-cineole main pharmacological constituent exhibits as natural analgesic agent. Eucalyptus globulus-loaded micellar nanoparticle was developed via spontaneous emulsification technique and further evaluation for its analgesic efficacy study, in vivo analgesic activity assay in rats. The nanoemulsion system containing Eucalyptus-micelles was optimized at different surfactant types (Tween 40, 60 and 80) and concentrations (3.0, 6.0, 9.0, 12.0, 15.0, and 18.0 wt. %). These formulations were characterized by thermodynamically stability, viscosity, micelles particle size, pH, and morphology structure. The spontaneous emulsification technique offered a greener micelles formation in nanoemulsion system by slowly titrated of organic phase, containing Eucalyptus globulus (active compound), grape seed oil (carrier oil) and hydrophilic surfactant into aqueous phase, and continuously stirred for 30 min to form a homogeneity solution. The characterizations evaluation revealed an optimized formulation with Tween 40 surfactant type at 9.0 wt. % of surfactant concentration promoted the most thermodynamic stability, smaller micelles particle size (d = 17.13 ± 0.035 nm) formed with spherical shape morphological structure, and suitable in viscosity (≈2.3 cP) and pH value (6.57) for transdermal purpose. The in vivo analgesic activity assay of optimized emulsion showed that the transdermal administration of micellar nanoparticle of Eucalyptus globulus on fore and hind limb of rats, possessed the central and peripheral analgesic effects by prolonged the rats pain responses towards the heat stimulus after being put on top of hot plate (55 °C), with longest time responses, 40.75 s at 60 min after treatment administration. Thus, this study demonstrated that micellar nanoparticle of Eucalyptus globulus formed in nanoemulsion system could be promising as an efficient transdermal nanocarrier for the analgesic therapy alternative.
To investigate the antifungal activity of conventional chitosan and chitosan-loaded nanoemulsions against anthracnose caused by Colletotrichum spp. isolated from different tropical fruits.
Theranostics has the potential to revolutionize the diagnosis, treatment, and prognosis of cancer, where novel drug delivery systems could be used to detect the disease at an early stage with instantaneous treatment. Various preclinical approaches of nanoemulsions with entrapped contrast and chemotherapeutic agents have been documented to act specifically on the tumor microenvironment (TME) for both diagnostic and therapeutic purposes. However, bringing these theranostic nanoemulsions through preclinical trials to patients requires several fundamental hurdles to be overcome, including the in vivo behavior of the delivery tool, degradation, and clearance from the system, as well as long-term toxicities. Here, we discuss recent advances in the application of nanoemulsions in molecular imaging with simultaneous therapeutic efficacy in a single delivery system.
Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE) has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ)/kg. TQRFNE and distilled water (DW) as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW) group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.
There is an increasing trend among pharmaceutical industries to use natural bioactive materials as medicinal agents and to use new technologies such as self-nanoemulsifying systems. The solubility and bioavailability of poorly soluble drugs can be enhanced by self-nanoemulsifying systems. Swietenia oil is frequently used because of its antimicrobial, antimutagenic, and anticancer bioactive medical properties. This study was conducted to develop self-nanoemulsifying systems for Swietenia oil that will enhance the anti-inflammatory activity of the oil. The self-emulsifying systems developed for Swietenia oil in this study were constructed using ternary phase diagrams and contained the nonionic surfactants Labrasol(®), Tween 20, Capmul(®), and Labrafil(®). The effect of these surfactants on the formulation was examined. The mean droplet size of Swietenia oil as well as their distribution, appearance, viscosity, and spreading times were studied to find the optimum formula, which contained droplets that were less than 200 nm. The next step was to test the anti-inflammatory properties of the optimum formula using a carrageenan-induced rat paw edema test. The results from this test were compared to the oil solution. Different oil/surfactants mixtures had various emulsification properties that were related to the size of their droplets. Tween 20 is a good surfactant to use in self-emulsifying systems because it produces droplets of nano-size. Mixtures of Capmul/Labrasol at a ratio of 2:1 and Labrafil/Tween 20 at a ratio of 1:2 were able to produce self-nanoemulsifying formulations containing Swietenia oil concentrations that ranged from 20%-50%. Nanoemulsion occurred when the size of the droplets fell below 200 nm with low size distribution (<0.3) after being gently mixed with water. It was found that the hydrophilic/lipophilic balance value affected the ternary phase diagram behavior of Swietenia oil and surfactants. In addition, the anti-inflammatory properties of Swietenia oil were greater in the self-nanoemulsifying systems than in the oil solution.
Ketoprofen is a potent non-steroidal anti-inflammatory drug has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of ketoprofen produces serious gastrointestinal adverse effects. One of the promising methods to overcome these adverse effects is to administer the drug through the skin. The aim of the present work is to evaluate the anti-inflammatory and analgesic effects from topically applied ketoprofen entrapped palm oil esters (POEs) based nanoemulsion and to compare with market ketoprofen product, Fastum(®) gel. The novelty of this study is, use of POEs for the oil phase of nanoemulsion. The anti-inflammatory and analgesic studies were performed on rats by carrageenan-induced rat hind paw edema test and carrageenan-induced hyperalgesia pain threshold test to compare the ketoprofen entrapped POEs based nanoemulsion formulation and market formulation. Results indicated that there are no significant different between ketoprofen entrapped POEs nanoemulsion and market formulation in carrageenan-induced rat hind paw edema study and carrageenan-induced hyperalgesia pain threshold study. However, it shows a significant different between POEs nanoemulsion formulation and control group in these studies at p<0.05. From these results it was concluded that the developed nanoemulsion have great potential for topical application of ketoprofen.
Oral paclitaxel (PTXL) formulations freed from cremophor® EL (CrEL) is always in utmost demand by the cancerous patients due to toxicities associated with the currently marketed formulation. In our previous investigation [Int. J. Pharm. 2014; 460:131], we have developed an oral oil based nanocarrier for the lipophilic drug, PTXL to target bioavailability issue and patient compliance. Here, we report in vivo antitumor activity and 28-day sub-chronic toxicity of the developed PTXL nanoemulsion. It was observed that the apoptotic potential of oral PTXL nanoemulsion significantly inhibited the growth of solid tumor (59.2 ± 7.17%; p
The study determined the effect of thymoquinone rich fraction (TQRF) and thymoquinone (TQ) in the forms of nano- and conventional emulsions on learning and memory, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble β-amyloid (Aβ) levels in rats fed with a high fat-cholesterol diet (HFCD). The TQRF was extracted from Nigella sativa seeds using a supercritical fluid extraction system and prepared into nanoemulsion, which later named as TQRF nanoemulsion (TQRFNE). Meanwhile, TQ was acquired commercially and prepared into thymoquinone nanoemulsion (TQNE). The TQRF and TQ conventional emulsions (CE), named as TQRFCE and TQCE, respectively were studied for comparison. Statin (simvastatin) and non-statin (probucol) cholesterol-lowering agents, and a mild-to-severe Alzheimer's disease drug (donepezil) were served as control drugs. The Sprague Dawley rats were fed with HFCD for 6 months, and treated with the intervention groups via oral gavage daily for the last 3 months. As a result, HFCD-fed rats exhibited hypercholesterolaemia, accompanied by memory deficit, increment of lipid peroxidation and soluble Aβ levels, decrement of total antioxidant status and down-regulation of antioxidants genes expression levels. TQRFNE demonstrated comparable effects to the other intervention groups and control drugs in serum biomarkers as well as in the learning and memory test. Somehow, TQRFNE was more prominent than those intervention groups and control drugs in brain biomarkers concomitant to gene and protein expression levels. Supplementation of TQRFNE into an HFCD thus could ameliorate memory deficit, lipid peroxidation and soluble Aβ levels as well as improving the total antioxidant status and antioxidants genes expression levels.