Insight into the Inclusion Complexation of Fluconazole with Sulfonatocalix[4]naphthalene in Aqueous Solution, Solid-State, and Its Antimycotic Activity.

The study aims to assess the interaction between fluconazole and sulfonatocalix[4]naphthalene towards enhancing its dissolution performance and antimycotic activity. A solubility study was carried out at different pH conditions, and the results revealed the formation of a 1:1 molar ratio fluconazole-sulfonatocalix[4]naphthalene inclusion complex with an AL type phase solubility diagrams. The solid powder systems of fluconazole-sulfonatocalix[4]naphthalene were prepared using kneaded and co-evaporation techniques and physical mixtures. DCS, PXRD, TGA-DTG, FT-IR, and in vitro dissolution performance characterize the prepared systems. According to physicochemical characterization, the co-evaporation approach produces an amorphous inclusion complex of the drug inside the cavity of sulfonatocalix[4]naphthalene. The co-evaporate product significantly increased the drug dissolution rate up to 93 ± 1.77% within 10 min, unlike other prepared solid powders. The antimycotic activity showed an increase substantially (p ≤ 0.05, t-test) antimycotic activity of fluconazole co-evaporate mixture with sulfonatocalix[4]naphthalene compared with fluconazole alone against clinical strains of Candida albicans and Candida glabrata. In conclusion, sulfonatocalix[4]naphthalene could be considered an efficient complexing agent for fluconazole to enhance its aqueous solubility, dissolution performance, and antimycotic activity.

Protective Effect of Portulaca oleracea Extract Against Lipopolysaccharide-Induced Neuroinflammation, Memory Decline, and Oxidative Stress in Mice: Potential Role of miR-146a and miR-let 7.

Neuroinflammation is an adaptive immune response to the central nervous system (CNS) injury induced by infection or toxins. MicroRNAs (miRs) showed critical roles in neuroinflammation as either proinflammatory or anti-inflammatory molecules. Interestingly, Portulaca oleracea (purslane) is an edible plant capable of ameliorating several diseases, including headache, burns, and diabetes; however, its effect on the neuroinflammation-associated miRs was not previously investigated. This study aimed to investigate the effect of aqueous purslane extract on the neuroinflammation induced by lipopolysaccharide (LPS) in mice and to identify its effect on animal cognition, oxidative stress, and expressions of miR-146a and miR-let 7. Adult mice were divided into the following groups: Normal group, LPS group, and Purslane+LPS group. Novel target recognition test, brain histopathology, and measurement of oxidative stress and inflammatory markers were performed. The results showed that LPS group exhibited significant decline in the cognitive memory, brain histopathological injury and a decrease in the number of intact neurons compared to the normal group. Furthermore, the LPS group showed a significant increase in malondialdehyde concentration, whereas superoxide dismutase and catalase activities were decreased. The LPS group also showed an increase in the inflammatory markers tumor necrosis factor-α and nuclear factor kappa B and downregulation of miR-146a and miR-let 7 expressions in the brain cells compared to the normal group, P value <.05. Interestingly, all these changes were reversed by administration of the aqueous purslane extract. In conclusion, the aqueous purslane extract protected from LPS-induced neuroinflammation and memory decline in mice through antioxidant and anti-inflammatory effect where upregulation of miR-146a and miR-1et 7 expressions was involved.

Studying the Complex Formation of Sulfonatocalix[4]naphthalene and Meloxicam towards Enhancing Its Solubility and Dissolution Performance.

The interaction between meloxicam and sulfonatocalix [4] naphthalene was investigated to improve the meloxicam solubility and its dissolution performance. Solubility behavior was investigated in distilled water (DW) and at different pH conditions. Besides, solid systems were prepared in a 1:1 molar ratio using coevaporate, kneading, and simple physical mixture techniques. Further, they were characterized by PXRD, FT-IR, DCS, and TGA. In vitro dissolution rate for coevaporate, kneaded, and physical mixture powders were also investigated. Solubility study revealed that meloxicam solubility significantly increased about 23.99 folds at phosphate buffer of pH 7.4 in the presence of sulfonatocalix [4] naphthalene. The solubility phase diagram was classified as AL type, indicating the formation of 1:1 stoichiometric inclusion complex. PXRD, FT-IR, DCS, and TGA pointed out the formation of an inclusion complex between meloxicam and sulfonatocalix [4] naphthalene solid powders prepared using coevaporate technique. In addition, in vitro meloxicam dissolution studies revealed an improvement of the drug dissolution rate. Furthermore, a significantly higher drug release (p ≤ 0.05) and a complete dissolution was achieved during the first 10 min compared with the other solid powders and commercial meloxicam product. The coevaporate product has the highest increasing dissolution fold and RDR10 in the investigated media, with average values ranging from 5.4-65.28 folds and 7.3-90.7, respectively. In conclusion, sulfonatocalix [4] naphthalene is a promising host carrier for enhancing the solubility and dissolution performance of meloxicam with an anticipated enhanced bioavailability and fast action for acute and chronic pain disorders.