•The antifusarium properties of phenols are preserved after incorporation in liposomes.•The phenolic compounds induce modifications in model lipid membranes.•The systems were characterized by NMR, ...DSC, FTIR, laser diffraction and cryo-TEM.
This study aimed to investigate the antifungal activity of liposomal systems containing Spirulina sp. LEB-18 phenolic extract (PE) against Fusarium graminearum (Fg) isolates. The interaction between PE and phosphatidylcholine-based liposomes was monitored by HATR-FTIR, NMR, DSC, and cryo-TEM. After encapsulation, the active principle was released slower than the free PE, a fact that makes the former very promising as a natural antifungal. The PE encapsulation in the liposomes was responsible for changes in the dynamics of specific regions. These compounds affected the membrane hydration degree, ordered the lipid phosphate region and increased the disorder of the acyl chain methylenes. These physico-chemical effects may be related to the strong inhibition of four Fg isolates. Results were discussed by correlating structural similarities, as well as the membrane effects of the PE under study on antifusarium activities, and those found in the literature, thus enabling the PE mechanisms of action to be analyzed.
The nose-to-brain delivery of neuroprotective natural compounds is an appealing approach for the treatment of neurodegenerative diseases. Nanoemulsions containing curcumin (CUR) and quercetin (QU) ...were prepared by high-pressure homogenization and characterized physicochemically and structurally. A negative (CQ_NE-), a positive (CQ_NE+), and a gel (CQ_NEgel) formulation were developed. The mean particle size of the CQ_NE- and CQ_NE+ was below 120 nm, while this increased to 240 nm for the CQ_NEgel. The formulations showed high encapsulation efficiency and protected the CUR/QU from biological/chemical degradation. Electron paramagnetic resonance spectroscopy showed that the CUR/QU were located at the interface of the oil phase in the proximity of the surfactant layer. The cytotoxicity studies showed that the formulations containing CUR/QU protected human nasal cells from the toxicity evidenced for blank NEs. No permeation across an in vitro model nasal epithelium was evidenced for CUR/QU, probably due to their poor water-solubility and instability in physiological buffers. However, the nasal cells' drug uptake showed that the total amount of CUR/QU in the cells was related to the NE characteristics (CQ_NE- > CQ_NE+ > CQ_NEgel). The method used allowed the obtainment of nanocarriers of an appropriate size for nasal administration. The treatment of the cells showed the protection of cellular viability, holding promise as an anti-inflammatory treatment able to prevent neurodegenerative diseases.
Curcumin (CUR) has properties that can be useful for the treatment of Alzheimer's disease. Such properties are the inhibition of amyloid-β-protein (Aβ) aggregation, Aβ-induced inflammation, and ...activities of β-secretase and acetylcholinesterase. However, previous studies have revealed that CUR exhibited low bioavailability and difficulties in reaching the brain.
To overcome such drawbacks, this study aims at developing nasal lipid nanocarriers loaded with CUR to effectively target the brain.
The lipid nanocarriers (NE) were prepared using the hot solvent diffusion associated with the phase inversion temperature methods. Physico-chemical and morphological characterizations and in vitro drug release of the nanocarriers were carried out. The CUR permeation/retention was analyzed in Franz-type diffusion cell using porcine nasal mucosa. Confocal laser scan and histopathological studies were also performed.
The results showed that the NE sizes ranged between 18 nm and 44 nm with negative zeta potential. The CUR content ranged from 0.24 to 1.50 mg/mL with an encapsulation efficiency of 99%. The profiles of CUR release indicated a biphasic kinetics. CUR-NE permeation across the porcine nasal mucosa was higher when compared to free CUR. These results have also been validated through an analysis on a confocal microscopy. In addition, no toxicity on the nasal mucosa has been observed in a histopathological analysis.
These results suggest that it is possible to develop NEs with a high content of CUR and small particle size. Such an encapsulation increases the potential of CUR permeation across the porcine nasal mucosa.
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Burns affect the skin and appendages, impair their function, and become favorable regions for bacterial infections. Owing to time-consuming and costly treatments, burns have been ...considered a public health problem. The limitations of the treatments used for burns have motivated the search for more efficient alternatives. Curcumin has several potential properties such as anti-inflammatory, healing, and antimicrobial activities. However, this compound is unstable and has low bioavailability. Therefore, nanotechnology could offer a solution for its application. This study aimed to develop and characterize dressings (or gauzes) impregnated with curcumin nanoemulsions that were prepared using two different techniques as a promising platform for skin burn treatment. In addition, the effect of cationization on curcumin release from the gauze was evaluated. Nanoemulsions were successfully prepared using two methods, ultrasound and a high-pressure homogenizer, with sizes of 135 nm and 144.55 nm, respectively. These nanoemulsions exhibited a low polydispersity index, adequate zeta potential, high encapsulation efficiency, and stability for up to 120 d. In vitro assays demonstrated a controlled release of curcumin between 2 and 240 h. No cytotoxicity was observed at concentrations of curcumin up to 75 µg/mL, and cell proliferation was observed. The incorporation of nanoemulsions in the gauze was successfully achieved, and the evaluation of curcumin release showed a faster release from cationized gauzes, whereas the non-cationized gauze promoted a more constant release.
(Lam.) DC extract-loaded nanoemulsions have demonstrated potential for wound healing, with promising effects on keratinocyte proliferation. We carried out the first in vivo investigation of the wound ...healing activity of a hydrogel containing
extract-loaded nanoemulsions. We prepared hydrogels by adding the gelling agent (Carbopol
Ultrez) to extract-loaded nanoemulsions (~250 nm in diameter) obtained by spontaneous emulsification. The final flavonoid content in formulation was close to 1 mg/mL, as estimated by ultra-fast liquid chromatography. Permeation/retention studies using porcine ear skin showed that flavonoids reached deeper layers of pig ear skin when it was damaged (up to 3.2 µg/cm² in the dermis), but did not reach the Franz-type diffusion cell receptor fluid. For healing activity, we performed a dorsal wound model using Wistar rats, evaluating the lesion size, anti-inflammatory markers, oxidative damage, and histology. We found that extract-loaded formulations promoted wound healing by increasing angiogenesis by ~20%, reducing inflammation (tumor necrosis factor α) by ~35%, decreasing lipid damage, and improving the re-epithelialization process in lesions. In addition, there was an increase in the number of blood vessels and hair follicles for wounds treated with the formulation compared with the controls. Our findings indicate that the proposed formulation could be promising in the search for better quality healing and tissue reconstruction.
ABSTRACT
Purpose
This study evaluates the advantage of the quercetin encapsulation in nanosized emulsion (QU-NE) administered orally in rats in order to demonstrate its anti-oedematous and ...antioxidant effects as well as its toxicity.
Methods
The nanocarriers were prepared using the hot solvent diffusion with the phase inversion temperature methods. The nanocarriers physicochemical properties were then investigated. The anti-edematous activity was tested using paw edema in rats. In addition, NF-kB expression in subcutaneous tissue of the paws was accessed by immunohistochemistry while the lipid peroxidation was analyzed in the liver by malondialdehyde reaction with thiobarbituric acid. Hematological, renal and hepatic toxicity as well as the genetic damage were also evaluated.
Results
The results demonstrated that QU-NE exhibited pronounced anti-oedematous property comparable to drug diclofenac. This effect was associated with NF-κB pathway inhibition. The lipid peroxidation was also only reduced in rats treated with QU-NE. Besides this, no genetic damage, hematological, renal or hepatic toxicities were observed after administration of QU-NE.
Conclusions
These results suggest that quercetin nanosized emulsion exhibits anti-oedematous and antioxidant properties and does not demonstrate toxic effects. This indicates that it has a potential application in the treatment of inflammatory diseases.
Achyrocline satureioides (Lam.) DC Asteraceae extracts (ASEs) have been investigated for the treatment of various skin disorders. This study reports the effects of ASE-loaded nanoemulsions (NEASE) on ...the cellular viability, death by necrosis, and migration of immortalized human keratinocytes (HaCaT cell line), as well as the irritant potential through the hen’s egg chorioallantoic membrane test (HET-CAM). NEASE exhibited a polydispersity index above 0.12, with a droplet size of 300 nm, ζ-potential of −40 mV, and content of flavonoids close to 1 mg/mL. No cytotoxicity of the ASE was observed on HaCaT by MTT assay (up to 10 µg/mL). A significant increase of HaCaT viability was observed to NEASE (up to 5 μg/mL of flavonoids), compared to treatment with the ASE. The necrosis death evaluation demonstrated that only NEASE did not lead to cell death at all the tested concentrations. The scratch assay demonstrated that NEASE was able to increase the cell migration at low flavonoid concentrations. Finally, the HET-CAM test proved the non-irritative potential of NEASE. Overall, the results indicate the potential of the proposed formulations for topical use in wound healing, in view of their promising effects on proliferation and migration in keratinocytes, combined with an indication of the absence of cytotoxicity and non-irritating potential.
Parkinson's disease is characterized by dopaminergic neuronal loss, mainly in the substantia nigra pars compacta. Currently, pharmacological treatment reduces the symptoms of the disease, however it ...does not affect its progression, and often leads to significant adverse effects. In this context, natural products have been explored as a potential source of neuroprotective substances. In this study, the neuroprotective potential of curcumin (CUR) and fish oil (FO) was evaluated against rotenone, which serves as a chemically induced experimental PD model. Male Swiss mice were treated with CUR, FO, CUR + FO or vehicle for seven days. On the eighth day, the animals began receiving rotenone in addition to the treatments for 30 days. At the end of the treatment, locomotor function, oxidative stress and toxicological markers were evaluated. Regarding motor parameters, CUR was able to reduce the number of slippages and bradykinesia in animals treated with rotenone. FO also improved motor coordination, but no additional benefits were observed when FO and CUR were associated. Interestingly, FO increased brain lipid peroxidation, which was attenuated when mice were treated with CUR, suggesting a beneficial effect of the association. In conclusion, CUR and FO possess protective properties against rotenone-induced neurotoxicity. However, the potential benefits of their combined use in relation to PD still require further studies. For example, investigating different doses and treatment durations, as well as evaluating parameters that assess neurodegeneration.
The flavonoid quercetin (QU) is a naturally occurring compound with several biological activities. However, the oral bioavailability of this compound is very low due to the high pre-systemic ...metabolism in the colon and liver and its low water solubility. In this context, the development of QU-loaded nanocarriers (NEs) is a promising approach to improve the drug oral bioavailability. This study investigates the variation of the concentration of 12-hydroxystearic acid-polyethylene glycol copolymer, lecithin and castor oil (CO) as to increase the amount of QU encapsulated while maintaining physicochemical characteristics described in previous studies. To better understand the ability to load and release the drug, we investigated the molecular interactions between QU and NE. Lipid-based NEs were prepared using CO as oily phase and PEG 660-stearate and lecithin as surfactants. Hot solvent diffusion and phase inversion temperature were methods employed to produce NEs. The QU-NEs were investigated for physicochemical characteristics and in vitro drug release. Molecular interactions between QU and the NEs were monitored through the complementary infrared (Fourier transform infrared) and NMR. The results revealed that it was possible to incorporate higher amounts of QU in a lipid-based NE with a reduced size (20 nm). The system developed allow a sustained release of QU probably due to the shell formed by the surfactants around the NE and the flavonoid ordering effect in the emulsion hydrophobic regions, which may reduce the system permeability.
Despite a considerable number of new antibiotics under going clinical trials, treatment of intracellular pathogens still represents a major pharmaceutical challenge. The use of lipid nanocarriers ...provides several advantages such as protection from compound degradation, increased bioavailability, and controlled and targeted drug release. Wheat germ agglutinin (WGA) is known to have its receptors on the alveolar epithelium and increase phagocytosis. The present study aimed to produce nanostructured lipid carriers with novel glycosylated amphiphilic employed to attach WGA on the surface of the nanocarriers to improve intracellular drug delivery. High-pressure homogenization was employed to prepare the lipid nanocarriers. In vitro, high-content analysis and flow cytometry assay was employed to study the increased uptake by macrophages when the nanocarriers were grafted with WGA. A lipid nanocarrier with surface-functionalized WGA protein (~200 nm, PDI > 0.3) was successfully produced and characterized. The system was loaded with a lipophilic model compound (quercetin; QU), demonstrating the ability to encapsulate a high amount of compound and release it in a controlled manner. The nanocarrier surface functionalization with the WGA protein increased the phagocytosis by macrophages. The system proposed here has characteristics to be further explored to treat intracellular pathogens.
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