Epilepsy is one of the most common neurological diseases, and current antiepileptic drugs fail to suppress seizure occurrence in around one third of epileptic patients. Curcumin is a phytochemical ...with promising effects on epilepsy treatment. However, its application has been hindered by its low bioavailability. In order to improve curcumin's anti-seizure properties, increasing its bioavailability, here we proposed to micronize the compound through supercritical carbon dioxide processing, a suitable green chemistry technique to prepare and modify material properties. Here we investigated the anti-seizure potential of the classical antiepileptic drug valproate, curcumin in its natural state, and micronized curcumin in a PTZ-induced seizure model in zebrafish (Danio rerio). Concerning seizure development, valproate, curcumin and micronized curcumin showed protective effects, slowing seizure development both in larvae and adult animals. Nevertheless, considering the occurrence of the tonic-clonic seizure stage, only valproate and micronized curcumin reduced it, both in larvae and adult zebrafish, unlike non-processed curcumin. Our obtained results are very promising, since micronized curcumin showed effects that are similar to a classic antiepileptic drug, reducing seizure occurrence and slowing seizure progression.
Epilepsy affects 50 million people around the world, and the patients experience cognitive, psychological and social consequences. Despite the considerable quantity of antiepileptic drugs available, ...30% of patients still suffer in seizure. Therefore, the advance in therapeutic alternatives is mandatory. Resveratrol has been attracting the attention of many researchers because of its pharmacological potential. However, despite its neuroprotective and anti-epileptic effects, clinical resveratrol use is impaired by its low bioavailability. Here, we applied the supercritical fluid micronization technology (SEDS) to overcome this deficit, and investigated the anticonvulsant potential of micronized resveratrol in a PTZ-induced seizure model in adult zebrafish (
Danio rerio
). SEDS permits obtaining significantly reduced particle size with a fine size distribution in comparison with the starting material. It can improve the pharmacotherapeutic efficacy. Our data showed that micronized resveratrol decreased the occurrence of the tonic–clonic seizure stage and slowed the development of the seizures in a similar manner of diazepam. Non-processed resveratrol was not able to protect the animals. Furthermore, diazepam decreased the locomotion and exploratory behavior. Differently from diazepam, the micronized resveratrol did not induce behavioral adverse events. In addition, our data showed that the PTZ-induced seizures increased the
c-fos
transcript levels following the neural excitability. However, the increase in
c-fos
levels was prevented by micronized resveratrol. In conclusion, our results demonstrate that the micronized resveratrol shows anticonvulsant effect, like the classical antiepileptic drug diazepam in a PTZ-induced seizure model. Excitingly, different from diazepam, micronized resveratrol did not provoke behavioral adverse events.
Epilepsy affects around 50 million people worldwide, and an important number of patients (30%) fail to respond to any available antiepileptic drug. Previous studies have shown that luteolin presents ...a promising potential as an anticonvulsant. On the other hand, different studies showed that luteolin does not promote anticonvulsant effects. Therefore, there is a lack of consensus about the use of luteolin for seizure control. Luteolin low bioavailability could be a limiting factor to obtain better results. Attractively, micronization technology has been applied to improve flavonoids bioavailability. Thus, the present study aimed to investigate the effects of luteolin on its raw form and micronized luteolin in a PTZ-induced seizure model in adult zebrafish (
Danio rerio
). Our results demonstrate that luteolin and micronized luteolin did not block PTZ-induced seizures in adult zebrafish. Also, luteolin and micronized luteolin did not provoke behavioral changes. Finally, our results show that 24 h after seizure occurrence, no changes were detected for
p70S6Kb
,
interleukin 1β
, and
caspase-3
transcript levels. Altogether, we failed to observe an anticonvulsant potential of luteolin in adult zebrafish, even in its micronized form. However, we recommend new studies to investigate luteolin benefits in epilepsy.
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•Cocrystals of resveratrol were prepared by CO2 antisolvent recrystallization (GAS technique).•Cocrystals were characterized by PXRD, FTIR, DSC and field emission scanning electron ...microscope (FESEM).•The obtained cocrystals present a higher rate of dissolution when compared with resveratrol.
Over the last years, resveratrol (RES), a phytoalexin found in grape skin, has received more attention due to its properties antioxidant, anticancer, anti-inflammatory, antimicrobial and cardioprotective. However, its use in food has been limited due to its poor solubility, instability and low bioavailability. Thus, the aim of study was to prepare cocrystals of resveratrol to improve solubility and dissolution rate using gas antisolvent (GAS) technique. The resveratrol cocrystals were prepared using isoniazid (INZ) and nicotinamide (NIC) as coformer by supercritical CO2 as antisolvent through the gas antisolvent technique. The coformers were selected from previous screening using anti-solvent liquid. The cocrystals were characterized by field emission scanning electron microscope (FESEM), infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). The RES-NIC cocrystal was evaluated in terms of dissolution rate, compared with resveratrol processed under the same conditions as the gas antisolvent.
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•Curcumin-nicotinamide cocrystal was formed.•Cocrystallization was performed with carbon dioxide as supercritical solvent.•Cocrystal showed 2 times greater dissolution rate in water ...than pure curcumin.•Cocrystal presented greater antinociceptive activity than curcumin.
Curcumin is a bioactive polyphenol, which presents several medicinal benefits such as antinociceptive, anti-inflammatory, anti-carcinogenic, antimalarial, and antioxidant activity. Despite the benefits, the main barrier in curcumin use by pharmaceutical industry is its low solubility in water medium and hence low bioavailability. The cocrystallization process is characterized by the incidence of molecular interactions between the active pharmaceutical ingredient and coformer that enables improvements in physicochemical properties such as solubility and bioavailability. The main objective of this work is to produce a curcumin-nicotinamide cocrystal by Cocrystallization with Supercritical Solvent (CSS) technique in order to increase curcumin water dissolution rate as well as antinociceptive/anti-inflammatory activities. Curcumin-nicotinamide cocrystal dissolution rate were about 2 times greater than pure curcumin in water medium. The cocrystallization process increased curcumin antinociceptive/anti-inflammatory potency probably due to alterations in its bioavailability. These results open new possibilities of use for curcumin cocrystals in pharmaceutical industries.
Epilepsy is a common neurological disorder which affects 50 million people worldwide. Patients with epilepsy may present cognitive deficits and psychological impairment. Currently, 30% of patients ...fail to respond to any available antiseizure drug, and a significant number of patients do not well tolerate the offered treatments. Then, it is necessary to find out alternatives for controlling epileptic seizures. Studies have shown that despite its neuroprotective effects, resveratrol shows poor anticonvulsant properties. Resveratrol analog, piceatannol, possesses higher biological activity than resveratrol and could be an alternative to control seizure. Thus, the present study investigated the effects of resveratrol and piceatannol in pentylenetetrazole-induced seizures in adult zebrafish (
Danio rerio
). Only the experimental positive control (diazepam) showed anticonvulsant effect in this study. In addition, no behavioral changes were observed 24 h after seizure occurrence. Finally, the expression of genes related to neuronal activity (
c-fos
), neurogenesis (
p70S6Ka and p70S6Kb
), inflammatory response (
interleukin 1β
), and cell apoptosis (
caspase-3
) did not change by pentylenetetrazole-induced seizures. Therefore, we failed to observe any anticonvulsant and neuroprotective potential of resveratrol and piceatannol in adult zebrafish. However, resveratrol and piceatannol benefits in epilepsy are not discharged, and more studies are necessary.
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•Philodendron bipinnatifidum is used in popular medicine with some pharmacological actions.•P. bipinnatifidum extract rich in β-sitosterol was obtained from ethyl acetate ...solvent.•Extract encapsulation process with PHBV was performed by the SEDS technique.•Spherical particles were obtained with efficiencies of about 90%.•GC/MS of the particles showed small variation in the composition of the extract.
Philodendron bipinnatifidum Schott ex Endl is a plant used in popular medicine with pharmacological actions already proven by scientific studies. The aim of this work was to investigate the application of Solution Enhanced Dispersion by Supercritical Fluids (SEDS) technique in the encapsulation of P. bipinnatifidum extract, rich in β-Sitosterol, in poly (hydroxybutyrate-co-hydroxyvalerate) biopolymer (PHBV). A 22 Central Composite Design (CCD) with 3 central points was used to assess the influence of extract concentration (5.0, 12.5 and 20.0 mg mL−1) and temperature (35.0, 37.5 and 40.0 °C) on particle size and encapsulation efficiency. Most of experiments obtained spherical particles and the highest encapsulation efficiency (89.56%) was verified using 20.0 mg mL−1 of extract concentration (ratio 1:1 extract and PHBV) and temperature of 35.0 °C. Also, the lowest medium particle size was achieved in these conditions, resulting in 0.622 ± 0.232 μm. The GC/MS analysis of the particles demonstrated that the process caused little variation in the chemical composition of the extract, maintaining its main constituents, such as the phytosterols campesterol, stigmasterol and β-sitosterol. The β-sitosterol compound had an increase of about 35% in its concentration in the extract after the encapsulation process. The results demonstrate the possibility of applying SEDS technique to encapsulate extracts with bioactive compounds of phytosterols class.
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•Micronization process potentiates the anticonvulsant effect of resveratrol.•Micronized resveratrol prevented the occurrence of tonic-clonic seizures.•Micronized resveratrol ...significantly slowed seizure development.•Micronized resveratrol prevented the behavioural alterations promoted by seizures.•Micronized resveratrol may be a safe drug candidate to be used during neurodevelopment.
Resveratrol is a natural non-flavonoid polyphenolic that has been emerging in epilepsy treatment. Despite its pharmacological properties, the poor bioavailability of resveratrol has been an important barrier that hinders its application as an anticonvulsant. The aim of this work was to improve resveratrol’s anticonvulsant effects by micronizing this compound through supercritical fluid micronization technology, which promotes an increase of the particles' surface area and allows significantly reduced particle size to be obtained. We obtained commercial and micronized resveratrol and investigated the anticonvulsant effects of resveratrol as commercially found and micronized resveratrol in a pentylenetetrazole-induced seizure model in zebrafish (Danio rerio) larvae. Diazepam was used as the positive control. Also, animals had their locomotor and exploratory activity analyzed 24 h after the seizure occurrence. The occurrence of the tonic-clonic seizure stage was only prevented by diazepam and micronized resveratrol, unlike the non-processed compound. The seizure development was significantly slowed by diazepam and micronized resveratrol, while non-micronized resveratrol was not able to increase the latency of seizure stages. In addition, diazepam and micronized resveratrol prevented the deleterious effects of pentylenetetrazole-induced seizures on animals’ locomotor and exploratory behaviour. Obtained data demonstrates that the micronization process potentiates the anticonvulsant effect of resveratrol. Micronized resveratrol achieved a similar effect to the classical drug diazepam, with the benefit that it may be a safe drug candidate to be used during the neurodevelopmental stage.
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•Curcumin+N-acetylcysteine cocrystals were prepared by cocrystallization with supercritical solvent technique (CSS).•Cocrystals were produced by solvent-free technique.•By DSC, XRD ...and FTIR it has been evidenced that the cocrystals were formed.•Cocrystallization provided cocrystals exhibiting a dissolution rate about 2 times higher than pure curcumin crystals.
Cocrystallization is a method that enables an improvement in physicochemical properties such as solubility, bioavailability, dissolution rate and stability. Curcumin (CUR) is bioactive ingredient known for its wide variety of medicinal benefits, such as anti-inflammatory, anti-carcinogenic, antimalarial and antioxidant activity, however its low solubility in water medium and hence low bioavailability represents a barrier in its use in food and pharmaceutical industry. This work aims to produce curcumin cocrystals by Cocrystallization with Supercritical Solvent (CSS) technique in order to improve curcumin water dissolution rate. N-acetylcysteine (NAC) was chose as coformer by previous screening using Liquid Assisted Grinding (LAG) technique. The cocrystals formations were confirmed through characterizations by Differential Scanning Calorimetry, Powder X-Ray Diffraction, Fourier Transform-Infrared Spectroscopy and Scanning Electron Microscopy. Cocrystals dissolution rate were about 2.2 times greater than pure curcumin dissolution in water medium, which opens new possibilities of use for these cocrystals in pharmaceutical and food industries.
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•The micronization process provided greater solubility of trans-resveratrol.•The micronization process increased the dissolution rate of the processed trans-resveratrol in relation to ...the non-micronized.•By PXRD and DSC it has been shown that micronized trans-resveratrol exhibits different crystalline structure of the raw compound.
The micronization process is characterized by the reduction of particle size towards obtaining changes in physical structure and increase the dissolution rate, which leads to increased solubility of the compound and consequently greater bioavailability. Trans-resveratrol is a nutraceutical compound with many biological properties; however, its use in the food, pharmaceutical and chemical industry is limited because of its low solubility in aqueous medium and hence low bioavailability. Due to the large potential of resveratrol, this work aims to investigate the properties of dissolution rate, solubility and in vitro antioxidant activity of micronized resveratrol by SEDS technique. The micronized compound increased by around 2.8 times its solubility in water while there was an increase in the dissolution rate of about 1.8 times. Results obtained in this work are promising as it enables the use of resveratrol in the food, pharmaceutical and chemical industry since the micronization process led to improved properties of the compound.
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