Curcumin and n-acetylcysteine cocrystal produced with supercritical solvent: characterization, solubility, and preclinical evaluation of antinociceptive and anti-inflammatory activities.

Curcumin presents a promising anti-inflammatory potential, but its low water-solubility and bioavailability hinder its application. In this sense, cocrystallization represents a tool for improving physicochemical properties, solubility, permeability, and bioavailability of new drug candidates. Thus, the aim of this work was to produce curcumin cocrystals (with n-acetylcysteine as coformer, which possesses anti-inflammatory and antioxidant activities), by the anti-solvent gas technique using supercritical carbon dioxide, and to test its antinociceptive and anti-inflammatory potential. The cocrystal was characterized by differential scanning calorimetry, powder X-ray diffraction and scanning electron microscopy. The cocrystal solubility and antichemotaxic activity were also assessed in vitro. Antinociceptive and anti-inflammatory activities were carried out in vivo using the acetic acid-induced abdominal writhing and carrageenan-induced paw oedema assays in mice. The results demonstrated the formation of a new crystalline structure, thereby confirming the successful formation of the cocrystal. The higher solubility of the cocrystal compared to pure curcumin was verified in acidic and neutral pH, and the cocrystal inhibited the chemotaxis of neutrophils in vitro. In vivo assays showed that cocrystal presents increased antinociceptive and anti-inflammatory potency when compared to pure curcumin, which could be related to an improvement in its bioavailability.

Micronized Resveratrol Shows Anticonvulsant Properties in Pentylenetetrazole-Induced Seizure Model in Adult Zebrafish.

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.