Characterization and Antiproliferative Activity of a Novel 2-Aminothiophene Derivative-ß-Cyclodextrin Binary System.

The novel 2-aminothiophene derivative 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN) has shown potential anti-proliferative activity in human cancer cell lines. However, the poor aqueous solubility of 6CN impairs its clinical use. This work aimed to develop binary 6CN-ß-cyclodextrin (ßCD) systems with the purpose of increasing 6CN solubility in water and therefore, to improve its pharmacological activity. The 6CN-ßCD binary systems were prepared by physical mixing, kneading and rotary evaporation methods and further characterized by FTIR, XRD, DSC, TG and SEM. In addition, molecular modeling and phase solubility studies were performed. Finally, MTT assays were performed to investigate the cytostatic and anti-proliferative effects of 6CN-ßCD binary systems. The characterization results show evident changes in the physicochemical properties of 6CN after the formation of the binary systems with ßCD. In addition, 6CN was associated with ßCD in aqueous solution and the solid state, which was confirmed by molecular modeling and the aforementioned characterization techniques. Phase solubility studies indicated that ßCD forms stable 1:1 complexes with 6CN. The MTT assay demonstrated the cytostatic and anti-proliferative activities of 6CN-ßCD binary systems and therefore, these might be considered as promising candidates for new anticancer drugs.

Development, Physicochemical Characterization and In Vitro Anti-Inflammatory Activity of Solid Dispersions of α,ß Amyrin Isolated from Protium Oilresin.

α,ß Amyrin (ABAM) is a natural mixture of pentacyclic triterpenes that has shown a variety of pharmacological properties, including anti-inflammatory effect. ABAM is isolated from Burseraceae oilresins, especially from the Protium species, which is commonly found in the Brazilian Amazon. This work aimed to develop solid dispersions (SD) of ABAM with the following hydrophilic polymers: polyvinylpyrrolidone (PVP-K30), polyethylene glycol (PEG-6000) and hydroxypropylmethylcellulose (HPMC). The SDs were prepared by physical mixture (PM), kneading (KND) and rotary evaporation (RE) methods. In order to verify any interaction between ABAM and the hydrophilic polymers, physicochemical characterization was performed by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), powder X-ray diffraction (XRD), thermogravimetry (TG) and differential scanning calorimetry (DSC) analysis. Furthermore, an in vitro anti-inflammatory assay was performed with ABAM alone and as SDs with the hydrophilic polymers. The results from the characterization analysis show that the SDs were able to induce changes in the physicochemical properties of ABAM, which suggests interaction with the polymer matrix. In vitro anti-inflammatory assay showed that the SDs improved the anti-inflammatory activity of ABAM and showed no cytotoxicity. In conclusion, this study showed the potential use of SDs as an efficient tool for improving the stability and anti-inflammatory activity of ABAM without cytotoxicity.

Inclusion Complexes of ß and HPß-Cyclodextrin with α, ß Amyrin and In Vitro Anti-Inflammatory Activity.

α, ß amyrin (ABAM) is a natural mixture of pentacyclic triterpenes that has a wide range of biological activities. ABAM is isolated from the species of the Burseraceae family, in which the species Protium is commonly found in the Amazon region of Brazil. The aim of this work was to develop inclusion complexes (ICs) of ABAM and ß-cyclodextrin (ßCD) and hydroxypropyl-ß-cyclodextrin (HPßCD) by physical mixing (PM) and kneading (KN) methods. Interactions between ABAM and the CD's as well as the formation of ICs were confirmed by physicochemical characterization in the solid state by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetry (TG) and differential scanning calorimetry (DSC). Physicochemical characterization indicated the formation of ICs with both ßCD and HPßCD. Such ICs were able to induce changes in the physicochemical properties of ABAM. In addition, the formation of ICs with cyclodextrins showed to be an effective and promising alternative to enhance the anti-inflammatory activity and safety of ABAM.

Amorphous solid dispersions of hecogenin acetate using different polymers for enhancement of solubility and improvement of anti-hyperalgesic effect in neuropathic pain model in mice.

Hecogenin acetate (HA) is an acetylated sapogenin that has shown potential antihyperalgesic activity, inhibiting descending pain and acting in opioid receptors. However, HA exhibits poor aqueous solubility, which may limit its application. This study aims to develop amorphous solid dispersions (ASD) using five hydrophilic polymers, to characterize them and to evaluate their antihyperalgesic activity. Physicochemical characterization was performed by X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Fourier Transformed Infrared (FTIR) spectroscopy. In order to evaluate the hyperalgesia of the ASD, sciatic nerve crush injury (NCI) was induced in mice followed by administration of the ASD, where three parameters were evaluated: mechanical and thermal hyperalgesia as well as grip strength. XRD and SEM showed that ASD of HA with HPMC obtained by kneading (KND) presented an amorphous profile, unlike the others polymers, indicating interaction between HA and HPMC. FTIR analysis evidenced the strong interaction between HA and HPMC. Although the results of mechanical hyperalgesia were slightly improved on the groups treated with ASD of HA with HPMC, the thermal hyperalgesia showed that the incorporation of HA into HPMC matrix significantly improved its antinociceptive activity.