Eduardo Pereira de Azevedo

With the advancement of in vivo studies and clinical trials, the pathogenesis of neurodegenerative diseases has been better understood. However, gaps still need to be better elucidated, which justifies the publication of reviews that explore the mechanisms related to the development of these diseases. Studies show that vitamin E supplementation can protect neurons from the damage caused by oxidative stress, with a positive impact on the prevention and progression of neurodegenerative diseases. Thus, this review aims to summarize the scientific evidence of the effects of vitamin E supplementation on neuroprotection and on neurodegeneration markers in experimental models. A search for studies published between 2000 and 2023 was carried out in the PubMed, Web of Science, Virtual Health Library (BVS), and Embase databases, in which the effects of vitamin E in experimental models of neurodegeneration were investigated. A total of 5669 potentially eligible studies were identified. After excluding the duplicates, 5373 remained, of which 5253 were excluded after checking the titles, 90 articles after reading the abstracts, and 11 after fully reviewing the manuscripts, leaving 19 publications to be included in this review. Experiments with in vivo models of neurodegenerative diseases demonstrated that vitamin E supplementation significantly improved memory, cognition, learning, motor function, and brain markers associated with neuroregeneration and neuroprotection. Vitamin E supplementation reduced beta-amyloid (Aβ) deposition and toxicity in experimental models of Alzheimer’s disease. In addition, it decreased tau-protein hyperphosphorylation and increased superoxide dismutase and brain-derived neurotrophic factor (BDNF) levels in rodents, which seems to indicate the potential use of vitamin E in preventing and delaying the progress of degenerative lesions in the central nervous system.

Cellulose acetate (ACT) is one of the most important cellulose derivatives due to its biodegradability and low toxicity, presenting itself as one of the main substitutes for synthetic materials in the development of wound dressing films. The incorporation of a N-acylhydrazonic derivative (JR19), with its promising anti-inflammatory activity, may represent an alternative for the treatment of skin wounds. This work aims to develop and to physicochemically and mechanically characterize ACT films containing JR19. The films were prepared using the ‘casting’ method and further characterized by thermoanalytical and spectroscopic techniques. In addition, mechanical tests and morphological analysis were performed. Thermogravimetry (TG) and differential scanning calorimetry (DSC) analyses showed that the thermal events attributed to excipients and films were similar, indicating the absence of physical incompatibilities between ACT and JR19. Infrared spectroscopy showed that JR19 was incorporated into ACT films. The characteristic band attributed to C≡N (2279 to 2264 cm⁻¹) was observed in the spectra of JR19, in that of the physical mixture of JR19/ACT, and, to a lesser extent, in the spectra of JR19 incorporated into the ACT film, suggesting some interaction between JR19 and ACT. X-ray diffraction (XRD) evidenced the suppression of the crystallinity of JR19 (diffraction peaks at 8.54°, 12.80°, 14.09°, 16.08°, 18.19°, 22.65°, 23.59°, 24.53°, 25.70°, 28.16° and 30.27°2θ) after incorporation into ACT films. The mechanical tests indicated the adequate integrity of the films and their resistance to bending. The morphological characterization showed JR19 crystals along with a homogeneously distributed porous structure throughout the surface of the films with an average diameter of 21.34 µm and 22.65 µm of the films alone and of those incorporating JR19F, respectively. This study was able to characterize the ACT films incorporating JR19, showing their potential to be further developed as wound healing dressings.

Chitosan films entrapped with the Mansoa hirsuta fraction (CMHF) was developed as a new dressing for wound care. The chromatographic profile of the M. hirsuta fraction (MHF) was evaluated by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and the results showed that MHF is rich in acid triterpenes. Physicochemical characterization of the films prepared using the solvent casting method was performed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetry (TGA), differential scanning calorimetry (DCS), scanning electron microscopy (SEM), atomic force microscopy (AFM), and mechanical properties. CMHF exhibited characteristic bands of both chitosan and MHF, revealing a physical mixture of both. CMHF presented an amorphous nature, thermostability, and dispersion of MHF in the chitosan matrix, resulting in a rough structure. Incorporation of M. hirsuta fraction into chitosan matrix favorably enhanced the mechanical performance and films thickness. The in vivo wound treatment with CMHF for seven days showed a characteristic area of advanced healing, re-epithelization, cell proliferation, and collagen formation. Furthermore, wound closure reached 100% contraction after 10 days of treatment with modulation of interleukins. The incorporation of M. hirsuta fraction into chitosan films was advantageous and showed great potential for stimulating wound repair and regeneration.

Cellulose is among the top 5 excipients used in the pharmaceutical industry. It has been considered one of the main diluents used in conventional and modern dosage forms. Therefore, different raw materials of plant origin have been evaluated as potential alternative sources of cellulose. In this context, Opuntia ficus-indica L. Miller (palma forrageira), a plant of the cactus family that has physiological mechanisms that provide greater productivity with reduced water requirements, is an interesting and unexplored alternative for extracting cellulose. By using this source, we aim to decrease the extraction stages and increase the yields, which might result in a decreased cost for the industry and consequently for the consumer. The aim of this work was to investigate the use of Opuntia ficus-indica L. Miller as a new source for cellulose extraction, therefore providing an efficient, straight forward and low-cost method of cellulose II production. The extraction method is based on the oxidation of the lignins. The obtained cellulose was identified and characterized by spectroscopic methods (FTIR and NMR), X-ray diffraction, thermal analysis (TGA-DTG and DSC) and scanning electron microscopy. The results confirmed the identity of cellulose and its fibrous nature, which are promising characteristics for its use in the industry and a reasonable substrate for chemical modifications for the synthesis of cellulose II derivatives with different physicochemical properties that might be used in the production of drug delivery systems and biomaterials.

α, β 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 β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) 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 βCD and HPβCD. 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.

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-β-cyclodextrin (βCD) systems with the purpose of increasing 6CN solubility in water and therefore, to improve its pharmacological activity. The 6CN-βCD 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-βCD binary systems. The characterization results show evident changes in the physicochemical properties of 6CN after the formation of the binary systems with βCD. In addition, 6CN was associated with βCD in aqueous solution and the solid state, which was confirmed by molecular modeling and the aforementioned characterization techniques. Phase solubility studies indicated that βCD forms stable 1:1 complexes with 6CN. The MTT assay demonstrated the cytostatic and anti-proliferative activities of 6CN-βCD binary systems and therefore, these might be considered as promising candidates for new anticancer drugs.

Complexation with cyclodextrins (CDs) is a technique that has been extensively used to increase the aqueous solubility of oils and improve their stability. In addition, this technique has been used to convert oils into solid materials. This work aims to develop inclusion complexes of Copaifera multijuga oleoresin (CMO), which presents anti-inflammatory activity, with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) by kneading (KND) and slurry (SL) methods. Physicochemical characterization was performed to verify the occurrence of interactions between CMO and the cyclodextrins. Carrageenan-induced hind paw edema in mice was carried out to evaluate the anti-inflammatory activity of CMO alone as well as complexed with CDs. Physicochemical characterization confirmed the formation of inclusion complex of CMO with both β-CD and HP-β-CD by KND and SL methods. Carrageenan-induced paw edema test showed that the anti-inflammatory activity of CMO was maintained after complexation with β-CD and HP-β-CD, where they were able to decrease the levels of nitrite and myeloperoxidase. In conclusion, this study showed that it is possible to produce inclusion complexes of CMO with CDs by KND and SL methods without any change in CMO’s anti-inflammatory activity.

Chagas disease is an endemic parasitic infection that occurs in 21 Latin American countries. New therapies for this disease are urgently needed, as the only two drugs available (nifurtimox and benznidazol) have high toxicity and variable efficacy in the disease’s chronic phase. Recently, a new chemical entity (NCE) named Pyranaphthoquinone (IVS320) was synthesized from lawsone. We report herein, a detailed study of the physicochemical properties and in vitro trypanocidal activity of IVS320. A series of assays were performed for characterization, where thermal, diffractometric, and morphological analysis were performed. In addition, the solubility, permeability, and hygroscopicity of IVS320 were determined. The results show that its poor solubility and low permeability may be due to its high degree of crystallinity (99.19%), which might require the use of proper techniques to increase the IVS320’s aqueous solubility and permeability. The trypanocidal activity study demonstrated that IVS320 is more potent than the reference drug benznidazole, with IC50/24 h of 1.49 ± 0.1 μM, which indicates that IVS320 has potential as a new drug candidate for the treatment of Chagas disease.

α,β 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.

Vascular thrombosis is a potentially fatal disease. Thrombolysis represents an efficient therapeutic option, although it still presents intrinsic bleeding risks. In order to minimize this problem, intra-thrombus injections, alone or associated with some kind of mechanical thrombectomy, have been used. In this work, a new approach to thrombolysis is presented, where the preparation, characterization and in vitro thrombolytic activity of a novel streptokinase foam are reported. Foams were prepared by mixing albumin solution with CO₂ at different volume ratios. Foam stability and apparent viscosity were the parameters used to characterize the foams. The volume ratio between CO₂ and albumin solution that yielded the samples with the best properties was used to prepare the thrombolytic foams, where streptokinase was used as the thrombolytic agent. The thrombolytic effect of this foam was assessed in vitro by delivering it intra-thrombus and the results were compared with those of the foam without streptokinase as well as those of a regular streptokinase solution. Both foam stability and viscosity increased as the ratio of CO₂:albumin solution increased and the 3:1 ratio was used to incorporate streptokinase. The in vitro thrombolytic activity study revealed that the streptokinase foam caused a 46.6 % of thrombus lysis after 30 min of experiment against 21 and 31 % of those of the foam without streptokinase and the regular streptokinase liquid solution, respectively. Thus, the use of CO₂:albumin foam enhanced the in vitro thrombolytic effect of streptokinase, which indicates its potential as a novel vehicle for carrying and delivering streptokinase to targeted thrombi.