Solid-lipid nanoparticles (SLN)s containing Zataria multiflora essential oil with no-cytotoxicity and potent repellent activity against Anopheles stephensi.

Malaria is still a global health concern with more than 400,000 death annually. Personal protection using mosquitoes' repellent is an effective prevention strategy, especially in endemic areas. The toxic effects of synthetics repellents and their adverse effects on fabricated goods have made the development of green repellent critical. In this study, ingredients of Zataria multiflora essential oil (ZMEO) were identified using GC-MS analysis. Solid-lipid nanoparticles containing ZMEO (1%) were prepared (SLN-ZMEO) using the high-pressure homogenizer method. The repellent activity of ZMEO and SLN-ZMEO was investigated using Klun and Debboun method and compared together. Besides, their cytotoxicity on a human skin normal cell line (HFFF2) was evaluated. Five major components of ZMEO were carvacrol (27.05%), thymol (26.452%), γ-terpinene (15.144%), o-cymene (13.584%), and α-pinene (9.483%). The SLN-ZMEO showed a spherical shape with a particle size of 134 ± 7 nm. Moreover, their polydispersity index (PDI), zeta potential and entrapment efficiency were determined as 0.24 ± 0.1, - 9.82 ± 0.95 mV and 64.6 ± 3.8%, respectively. Interestingly, the protection time of nanoformulation (93 ± 5 min) was three times longer than that of the non-formulated essential oil (29 ± 2 min). Interestingly, both samples did not show cytotoxicity on HFFF2. Therefore, the prepared nanoformulation can be used as a green and potent repellent.

Protective effects of melatonin solid lipid nanoparticles on testis histology after testicular trauma in rats.

Testicular traumatic injuries occur frequently, which can result in an alteration in spermatogenesis. These injuries can also cause oxidative stress and male infertility. Antioxidant efficiency of melatonin (MLT), known as a potent antioxidant, will be improved if used in a form of solid lipid nanoparticles (MLT-SLN). The aim of the current study is to evaluate the effect of MLT-loaded SLN on traumatic testis in rats. In this study 32 adult male Wistar rats were divided into 4 groups. Group 1 (sham group), right testicle was drawn out from the scrotum and returned without manipulation. Group 2, right testicle was dropped by 25 g sinker for 4 times. Group 3, animals were received a single dose (25 mg/kg) of MLT intraperitoneally after trauma. Group 4, animals were received a single dose of MLT-SLN intraperitoneally after trauma. Under anaesthesia, rats were sacrificed, and their testicles were removed three days after the surgery. After tissue processing, the sample sections were H&E stained. MLT and MLT-SLN could partially repair spermatogenesis by Johnson's criteria but the repairs were significant only in MLT-SLN group (P = 0.02). Trauma decreased seminiferous tubule diameter and its epithelium height. MLT could restore epithelium height (P ≤ 0.05) but its NPs improved both epithelium diameter (P ≤ 0.05) and thickness (P ≤ 0.001). The Malondialdehyde increased significantly in trauma group (P = 0.002), but decreased in MLT and NPs groups compared to trauma group (P = 0.098 and P = 0.002 respectively). This decrease was significant only in NPs group. Testicular trauma disturbed spermatogenesis, morphometric, and oxidative parameters. MLT and specially MLT-SLN improved traumatic damages.

Improved yeast delivery of fluconazole with a nanostructured lipid carrier system.

Despite the growing trends in the number of patients at risk for invasive fungal infections, management with current antifungal agents results in complications due to changes in the epidemiology and drug susceptibility of invasive fungal infections. In the present research fluconazole-loaded nanostructured lipid carriers were prepared using probe ultrasonication techniques and investigated the efficacy of the optimal formulation on a large number of Candida species. The morphology of the obtained nanostructured lipid carriers was characterized by transmission-electron microscopy. The minimum inhibitory concentrations (MIC) for the new formulations against strains of Candida were investigated using the Clinical and Laboratory Standards Institute document M27-A3 and M27-S4 as a guideline. The fluconazole-loaded nanostructured lipid carriers presented a spherical shape with a mean diameter, zeta potential and entrapment efficiency of 126.4±15.2nm, -35.1±3.0mV, and 93.6±3.5%, respectively. The drug release from fluconazole-loaded nanostructured lipid carriers exhibited burst-release behavior at the initial stage followed by sustained release over 24h. Using a new formulation of fluconazole led to a significant decrease in MICs for all Candida groups (P<0.05). Furthermore, C. albicans isolates showed more susceptibility to fluconazole-loaded nanostructured lipid carriers than C. glabrata and C. parapsilosis (P<0.05). The MIC50 drug concentration was obtained as 0.0625, 0.031 and 0.25µg/ml for fluconazole-resistant strains of C. albicans, C. glabrata, and C. parapsilosis, respectively. In conclusion, a novel delivery system which can be used as part of a strategy to improve the antifungal activity of fluconazole against various Candida strains with different susceptibilities to conventional formulations of fluconazole was evaluated.

Antileishmanial Activity of Lavandula angustifolia and Rosmarinus Officinalis Essential Oils and Nano-emulsions on Leishmania major (MRHO/IR/75/ER).

BACKGROUND: The aim of present study was to evaluate antileishmanial effects of Lavandula angustifolia (L. angustifolia) and Rosmarinus officinalis (R. officinalis) medicinal plants essential oils and nano-emulsions on Leishmania major (L. major). METHODS: The present study was performed in Leishmaniasis Reference Lab at Mazandaran University of Medical Sciences, Iran during 2016-2017. The IC50 values were calculated in both the promastigote and amastigote stages in J774 macrophage in comparison with meglumine antimoniate (MA) as positive control. In addition, cytotoxicity effects of essential oils and nano-emulsions prepared from both plants against macrophages were evaluated. RESULTS: Both essential oil and nano-emulsion of Lavander and Rosemary showed anti-leishmania activity on promastigote with IC50=0.11 µl/mL, IC50=0.26 µl/mL, and IC50=0.08 µl/mL respectively. Moreover, during amastigote assay, Lavander and Rosemary essential oils and nano-emulsion were effective at least in concentration of 0.12 µl/mL and 0.06 µl/mL (P=0.0001) respectively, on mean infected macrophages (MIR) and amastigotes in macrophages (P=0.0001). Additionally, cytotoxicity assay against macrophage revealed no toxicity on the host cells at IC50 concentrations. CONCLUSION: The nano-emulsions of both plants were more effective than essential oil in both MIR and amastigote. However, in comparison with MA, the Lavander essential oil is more effective in reducing MIR. Rosemary nano-emulsion reduced MIR significantly more than MA in concentration of 0.25 µl/mL (P<0.001). Further investigations are recommended to evaluate the effect of these medicinal plants in murine models.

Spironolactone loaded nanostructured lipid carrier gel for effective treatment of mild and moderate acne vulgaris: A randomized, double-blind, prospective trial.

Spironolactone (SP) known as an anti-androgen drug, has been proven to be effective in treatment of acne. The quest to minimize the unnecessary systemic side effects associated with the oral drug administration of spironolactone, has led to a growing interest of loading SP on lipid nanoparticles to deliver the drug in a topical formulation. The aim of the current investigation was to prepare and compare the performance of SP loaded nanostructured lipid carrier (SP-NLC) and SP alcoholic gels (SP-ALC) on two groups of respective patient populations, group A and group B in the treatment of mild to moderate acne vulgaris. The results showed that SP-NLCs were spherical in shape with an average diameter of ∼240nm. The polydispersity index (PI) and zeta potential of these nanoparticles were 0.286 and -21.4 respectively. The gels showed non-Newtonian independent pseudoplastic and shear thinning behavior. The SP-NLCs was not toxic to fibroblast cell strains at the 24 and 48h periods. Results showed that the mean number of total lesions (37.66±9.27) and non-inflammatory lesions (29.26±7.99) in group A significantly decreased to 20.31±6.58 (p<0.05) and to 13.95±5.22 (p<0.05) respectively. A similar pattern was observed for group B where the mean number of total lesions and non-inflammatory lesions reduced from 33.73±9.40 to 19.13±5.53 (p<0.05) and from 25.65±8.12 to 13.45±4.48 (p<0.05) respectively. The total lesion count (TLC) was significantly decreased from 37.16±9.28 to 19.63±6.36 (for group A; p<0.071) and 32.60±9.32 to 18.33±5.55 (for group B; p<0.05) respectively. After treatment with SP-NLC for 8 weeks, the water content of the skin significantly (p<0.05) increased from 37.44±8.85 to 45.69±19.34 instrumental units. Therefore, the SP-NLC gel may help in controlling acne vulgaris with skin care benefits.

Time to overcome fluconazole resistant Candida isolates: Solid lipid nanoparticles as a novel antifungal drug delivery system.

Antifungal therapy results in complications in management due to changes in the patterns of epidemiology and drug susceptibility of invasive fungal infections. In this study, we prepared fluconazole-loaded solid lipid nanoparticles (FLZ-SLNs) and investigated the efficacy of the optimal formulation on fluconazole (FLZ)-resistant strains of several Candida species. FLZ-SLN was produced using probe ultrasonication techniques. The morphology of the obtained SLNs was characterized by field emission scanning electron microscopy. The minimum inhibitory concentrations for the new formulations against fluconazole-resistant strains of Candida were investigated using CLSI document M27-A3. The FLZ-SLNs presented a spherical shape with a mean diameter, zeta potential and entrapment efficiency of 84.8nm, -25mV and 89.6%, respectively. The drug release from FLZ-SLNs exhibited burst release behaviour at the initial stage (the first 30min) followed by a sustained release over 24h FLZ-resistant yeast strains behaved as susceptible strains after treatment with FLZ-SLNs (≤8µg/ml). The MIC50 drug concentrations were 2µg/ml, 1µg/ml and 2µg/ml for FLZ-resistant strains of Candida albicans, Candida parapsilosis and Candida glabrata, respectively. In this study, we evaluated novel delivery systems for combating Candida strains that exhibit low susceptibility against the conventional formulation of FLZ as a first-line treatment.

The Effect of Tween 20, 60, and 80 on Dissolution Behavior of Sprionolactone in Solid Dispersions Prepared by PEG 6000.

PURPOSE: Solid dispersions have been efficient in improving the dissolution rate and bioavailability of hydrophobic drugs. The aim of the present study was enhancement of the dissolution profile of Spironolactone using solid dispersion. METHODS: Spironolactone solid dispersions (1:1, 1:2 and 2:1 drug: carrier weight ratio) were prepared by polyethylene glycol (PEG) 6000 as a carrier by hot melt method. The influence of several amounts of Tween 20, 60, and 80 were also studied. The dissolution profile was evaluated by USP Apparatus II. RESULTS: The results showed that solid dispersions were efficacious to enhance the dissolution rate of Spironolactone in water; and the procedure indicated that there was an increase in dissolution rate for solid dispersions containing the surfactant Tweens. The solid dispersions were evaluated using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and Differential Scanning Calorimetry (DSC) studies; and the results showed no complex formation or change in crystal shape of drug. CONCLUSION: It is concluded that solid dispersion technique can be successfully used for improvement of dissolution of Spironolactone.