Os fármacos podem ser encontrados nos estados cristalino, co-cristalino ou amorfo, sendo que o estado cristalino geralmente apresenta menor solubilidade em água e, consequentemente, reduzida biodisponibilidade. A manipulação do estado sólido representa uma estratégia promissora para melhorar a taxa de dissolução e a biodisponibilidade de fármacos classificados nos grupos II e IV do Sistema de Classificação Biofarmacêutica (SCB). Nesse contexto, as dispersões sólidas amorfas (DSA) destacam-se como uma tecnologia eficaz, ao promover a conversão do fármaco do estado cristalino para o amorfo, com o auxílio de um agente dispersante. O presente estudo trata-se de uma revisão narrativa da literatura, elaborada a partir de uma estratégia de busca estruturada em bases de dados científicas. Os artigos selecionados abordam aspectos fundamentais como solubilidade, dissolução, modificação do estado sólido e seu impacto na biodisponibilidade oral. Adicionalmente, a revisão explora ainda as definições e classificações das DSA, os métodos empregados na sua obtenção, técnicas de caracterização e os desafios relacionados à estabilidade físico-química desses sistemas farmacêuticos ao longo do tempo.
Schistosomiasis currently relies on the long-term use of a single drug, praziquantel (PZQ). Artesunic acid (AcART) has emerged as a promising alternative, as it is efficient against juvenile worms. However, like PZQ, it has low aqueous solubility. Self-Emulsifying Drug Delivery Systems (SEDDS) and Lyotropic Liquid Crystal Nanoparticles (NPs-LLC) present advantages for oral administration, including enhanced solubility and protection of the drug from first-pass metabolism. This study compared the in vitro and in vivo efficacy of AcART incorporated into SEDDS and NPs-LLC against juvenile and adult worms of two different Schistosoma mansoni strains. In vitro phenotypic assays with AcART incorporated into both SEDDS and NPs-LLC demonstrated a progressive decrease in parasite viability, significant tegumental changes, inhibition of oviposition, and 100 % mortality at a concentration 6.25 µg/mL. In vivo treatments performed at 21- and 60-days post-infection with AcART formulated in SEDDS and NPs-LLC led to a significant reduction in worms' burden and eggs eliminated in feces compared to the control group. The SEDDS nanosystems (drug-free) influenced the in vitro results, whereas the NPs-LLC (drug- free) did not influence any of the assays. Our findings demonstrate that these nanosystems enhance the efficacy of AcART against both BH and SE strains of S. mansoni, even at substantially lower concentrations than conventional formulations. This represents an innovative approach for the treatment of schistosomiasis, with potential applications to other neglected diseases.
Abstract This study focuses on the development and characterization of gelatin-based membranes with varying concentrations of poly(ethylene glycol) (PEG) as potential cost-effective skin substitutes for burn wound treatment. In lowand middle-income countries, where burn injuries pose a significant public health challenge, affordable solutions are crucial. Gelatin/PEG membranes were prepared with PEG concentrations ranging from 3% to 30%. Fourier Transform Infrared Spectroscopy (FT-IR) analysis demonstrated an interaction between gelatin and PEG, indicating cohesive integration through hydrogen bonding, while mechanical tests showed an initial enhancement in Young’s modulus up to a 10% PEG concentration, suggesting improved interaction. Swelling tests revealed that higher PEG concentrations led to increased swelling capacity and reduced mass loss. Scanning electron micrographs supported these findings, showing an irregular surface and the formation of PEG agglomerates, which contributed to improved mechanical resistance. These gelatin-PEG membranes offer a promising avenue for cost-effective skin substitutes, addressing the need for accessible solutions in burn wound care, especially in resource-constrained settings. Further research and clinical validation are essential to assess their efficacy and safety in practical applications, potentially revolutionizing burn wound treatment.
This in vitro study aimed to assess the biocompatibility and osteogenic inducing properties of a new scaffold composed of chitosan, collagen type I, and hyaluronic acid. For in vitro assays, pre-osteoblastic immortalized cells were cultivated in standard medium (SD) and osteogenic medium (OM) in the following groups: a) Control (C) – cells cultured directly on the polystyrene plate, and b) Chitosan + Collagen type I + Hyaluronic Acid (CH + COL + HA) - cells cultured in a scaffold produced by the association of type I collagen, chitosan and hyaluronic acid. Cells in CH+COL+ HA scaffold presented metabolic activity similar to the control group. After 14 days, the CH+ COL+ HA scaffold induced a higher mineral nodule deposition compared than the control group, regardless of the cultured condition (SD or OM medium). In addition, the CH + COL + HA scaffold itself increased of the alkaline phosphatase activity and mRNA levels for Runx2 and Ocn genes, which occurred earlier than control group. Based on the results, it is possible to conclude that the dense lamellar scaffold composed of CH/COL (type I)/HA stimulated osteogenic phenotype maturation of cells and can be a promising material for future bone regenerative approaches.
Among non-communicable diseases, cardiovascular diseases are the most prevalent, accounting for approximately 17 million deaths per year. Despite conventional treatment, cardiac tissue engineering emerges as a potential alternative for the advancement and treatment of these patients, using biomaterials to replace or repair cardiac tissues. Among these materials, gelatin in its methacrylated form (GelMA) is a biodegradable and biocompatible polymer with adjustable biophysical properties. Furthermore, gelatin has the ability to replace and perform collagen-like functions for cell development in vitro. The interest in using GelMA hydrogels combined with nanomaterials is increasingly growing to promote the responsiveness to external stimuli and improve certain properties of these hydrogels by exploring the incorporation of nanomaterials into these hydrogels to serve as electrical signaling conductive elements. This review highlights the applications of electrically conductive nanomaterials associated with GelMA hydrogels for the development of structures for cardiac tissue engineering, by focusing on studies that report the combination of GelMA with nanomaterials, such as gold and carbon derivatives (carbon nanotubes and graphene), in addition to the possibility of applying these materials in 3D tissue engineering, developing new possibilities for cardiac studies.
Praziquantel (PZQ) is the drug of choice for treating cestode and trematode infections, and it is currently the only option against schistosomiasis. Artesunic acid (AcART) is effective against several parasites and has emerged as an alternative for schistosomiasis treatment. However, AcART and PZQ have limited bioavailability due to poor water solubility, low permeability, and rapid cell clearance. To address these challenges, this study aimed to develop self-emulsifying drug delivery systems to develop SEDDS and NPs-LLC to overcome the low water solubility affecting AcART and PZQ bioavailability. The study involved validating the HPLC analytical methodology for AcART, SEDDS, and NPs-LLC formulations, and conducting physicochemical characterization and ex-vivo intestinal permeation assays. The composition of formulations was determined by the solubility balance of AcART and PZQ. The drug content ranged between 83 and 90 %. The anionic zeta potential was attributed to Myverol (R), and the particle diameter increased slightly after the drug incorporation, while the polydispersity index indicated the relatively narrow particle size distribution. Additionally, the DSC thermogram confirmed that PZQ and AcART are in solution within SEDDS and NPs-LLC. The FTIR analysis suggests that components of SEDDS and NPs-LLC and drugs do not react to form new chemical species. The selection of specific compound formulations was based on achieving the best solubility balance. The nanostructures were stable and exhibited a surface charge favorable to mucosal permeation, with slightly superior performance for SEDDS. The innovative formulations, SEDDS and NPs-LLC, are suitable and effective carriers for AcART and PZQ.
The chemical processing of polymeric mixtures is a promising alternative for designing materials with new characteristics for biomedical applications. This work proposed to produce and characterize polymeric mixtures obtained using polyethylene glycol (PEG400 or PEG4000) with poly (L-co-D, L lactic acid)/PLDLA for biomedical use. The mixtures were prepared by the casting method. Characterizations were performed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), mechanical properties (perforation, resilience, elastic modulus, plastic deformation, tensile strength and mucoadhesion) and in vitro biodisintegration studies. The results obtained by FTIR and DSC suggest that the chemical interactions that generate the mixtures between the polymers occurred through hydrogen bonds and/or dipole-dipole interactions. Chemical interactions created compounds that were more hydrophilic and had different rearrangements when using PEG400 or PEG4000 in the mixture. The mechanical tests showed changes in the resistance of the materials, highlighting the exponential value of plastic deformation of PLDLA/PEG400, significantly increasing the plasticity of this structure by 111-fold about PLDLA/PEG4000. In the biodisintegration study, after 120 hours, greater mass loss was observed for PLDLA/PEG4000 (68.82 ± 1.46%). Hydrolytic disintegration did not influence pH values, which remained between 7.34 and 7.41 during the study. In conclusion, these mixtures can provide valuable characteristics to produce a biocompatible biomedical device with properties to support tissue regeneration, where the issue of plastic deformation is necessary in collaboration with the formation of pores, after PEG dissolution in vivo.
New wound dressings based on polymeric membranes have been widely exploited for clinical applications to assist in the healing process and prevent additional complications (e.g., bacterial infections). Here we propose the development of a new production method of polymeric membranes based on chitosan, incorporating glycolic extract of Aloe vera with joint synthesis of silver nanoparticles for use as a new bioactive dressing. The membranes were obtained by casting technique, and their morphological, physicochemical characteristics, degree of swelling, degradation profile and antimicrobial activity evaluated. Morphological analyzes confirmed the synthesis and presence of silver nanoparticles in the polymeric membrane. The chemical compatibility between the materials was demonstrated through thermal analysis (TGA and DSC) combined with ATR-FTIR tests, showing the complexation of the membranes (Mb-Ch-Ex.Av-NPs). All membranes were characterized as hydrophilic material (with a contact angle (ө) < 90°); however, the highest degree of swelling was obtained for the chitosan. (Mb-Ch) membrane (69.91 ± 5.75
Graphene is a two-dimensional carbon material with unique properties, such as high thermal and electrical conductivity, mechanical strength, elasticity, and biocompatibility. The methods used to synthesize graphene affect its structural properties, including flaws, layer count, crystalline domain size, and impurities, ultimately affecting the properties and performance of graphene-based materials. This review aims to analyze the methods used to characterize graphene, using both ISO/IEC standards and current literature as references. The discussed techniques are diverse, yet complementary, and include ultraviolet–visible spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray absorption near edge structure, atomic force microscopy, scanning electron microscopy, transmission electron microscopy, the Brunauer–Emmett–Teller method, thermogravimetric analysis, in-line four-point probe, resonant cavity and terahertz time-domain spectroscopy, besides an alternative method to determine the graphene domain. By employing rigorous characterization techniques, researchers and industry professionals can ensure the reliability, effectiveness, and trustworthiness of graphene-based materials for various applications.
Numerous reports suggest curcumin can potentially treat neurological disorders like Parkinson's and Alzheimer's. However, the effectiveness of curcumin is not fully utilized due to factors such as low chemical stability, poor water solubility, and physiological barriers, which result in poor bioavailability. Curcumin's low plasma and tissue levels are primarily caused by poor absorption, rapid metabolism, and rapid systemic elimination. Pharmaceutical engineering has utilized nanoparticulate dosage forms to improve drug delivery and overcome curcumin's pharmacokinetics and pharmacodynamics obstacles. This can include increasing the solubility and permeability, enhancing retention time, modifying the release, and targeting drugs to the brain and escaping the endothelial reticulum. Herein lies a wide range of applications in pharmaceutical technology and nanotechnology, particularly in target drug delivery systems, to overcome the low curcumin bioavailability. Small-size structures have unique characteristics that make them highly suitable for curcumin delivery and targeting objectives. Therefore, liposomes, self-emulsifying drug delivery systems (SEDDS), liquid crystal polymeric and lipid nanoparticles, dendrimers, and mesoporous silica nanoparticles can be developed for all these specific purposes.
The aim of this study was to develop a dense lamellar scaffolding composed by collagen (COL), silk fibroin (SF) and polyethylene glycol 400 (PEG 400) and evaluate the influence of freezing parameters (-80,-50, and-18 degrees C) associated with its plastic compression. The physicochemical characterization of the developed scaffolds was done by mechanical and morphological properties. Fourier Transform Infrared Spectroscopy (FTIR) and Differential scanning calorimetry (DSC) showed crosslinking between PEG and polymers, the change in the COL structure confirming electrostatic interaction between functional groups, in addition to beta-sheet conformations of SF induced by lyophilization. Morphological analyzes showed changes in pore size between 69.8 and 97.3 mu m (-80), 73.7-121.8 mu m (-50) and 84.3-134.0 mu m (-18). Interconnectivity was found to be 60.83% (-80), 62.62% (-50) and 66.76% (-18), confirming the pore connectivity which is key for cell growth. The percentage of closed pores of 0.19% (-80), 0.13% (-50) and 0.11% (-18) were recorded, together with the pore volume of 12.97 mm-3 (-80), 2.31 mm-3 (-50) and 1.61 mm-3 (-18). The freezing significantly modulated the aniso-tropic degree, obtaining anisotropic (-18 degrees C), partially anisotropic (-50 degrees C), and isotropic (-80 degrees C) scaffolds. The scaffolds showed similar swelling values after 120 h, however, a lower rate of biodisintegration was confirmed by the scaffold COL-SF-PEG 400 (-80). Hydrolytic degradation did not influence the pH values, which remained between 7.39 and 7.45 over the same timeframe. The freezing rate changed the mechanical properties, showing greater resistance to the scaffold COL-SF-PEG 400 (-50), except for elasticity. Considering the results of this study, the different freezing rates were able to modulate scaffolds with unique characteristics and of interest for potential tissue engineering applications, with an emphasis in obtaining anisotropic or isotropic structures.
Cardiovascular diseases (CVD) compromise the quality of life and have become the leading cause of death worldwide. In the past few decades, emerging therapies for CVD have been investigated by promoting cardiac repair using various biomaterials. Among them, scaffolds that recapitulate the extracellular matrix facilitating the electroconductivity and interconnectivity among the cells have attracted researchers to improve and enhance the patient’s quality of life. This review addresses the recent advances of electrically conductive nanomaterials and nanocomposites to be applied in cardiac tissue engineering. Interdisciplinarity efforts toward innovation in bioengineering launch new and improved biomaterials for clinical applications, which are expected to impact soon.
Benzene, toluene, ethylbenzene and xylene (BTEX) are toxic petroleum hydrocarbons pollutants that can affect the central nervous system and even cause cancer. For that reason, studies regarding BTEX degradation are extremely important. Our study aimed evaluate the microorganism Bacillus subtilis as a tool for degrading petroleum hydrocarbons pollutants. Assays were run utilizing water or soil distinctly contaminated with gasoline and diesel oil, with and without B. subtilis. The ability of B. subtilis to degrade hydrophobic compounds was analyzed by Fourier-Transform Infrared Spectroscopy (FTIR) and gas chromatography. The FTIR results indicated, for water assays, that B. subtilis utilized the gasoline and diesel oil to produce the biosurfactant, and, as a consequence, performed a biodegradation process. In the same way, for soil assay, B. subtilis biodegraded the diesel oil. The gas chromatography results indicated, for gasoline in soil assay, the B. subtilis removed BTEX. So, B. subtilis was capable of degrading BTEX, producing biosurfactant and it can also be used for other industrial applications. Bioremediation can be an efficient, economical, and versatile alternative for BTEX contamination.
The objective of the study was to evaluate the encapsulation of seeds of tropical forest species with cellulose gel (CG) from Vitis vinifera and sodium alginate, with and without biostimulant, in order to optimise its size, shape and performance for direct seeding. Four species used in direct seeding were selected, i.e., Bixa orellana L., Mimosa bimucronata (DC.) Kuntze, Trema micrantha (L.) Blume and Psidium guajava L.. The experimental design was completely randomised with eight treatments and four repetitions of 100 seeds each. Encapsulation affected the physical quality of the seeds, however, it facilitated their handling and visualisation in germination tests, especially for T. micrantha, with a 4-fold increase in size with alginate gel and 2-fold with CG. Sodium alginate performed better than CG, synchronising the growth of B. orellana seedlings. The biostimulant showed potential to synchronise germination, vigor and seedling growth when associated with dormancy break for M. bimucronata, and promoted seedling growth for P. guajava. Sodium alginate gel has potential for seed enhancement, while CG encapsulation needs to be improved in relation to its physical characteristics, requiring further studies. The biostimulant can be recommended for enhancing uniformity of seed emergence in direct seeding.
Intelligent curatives have been increasingly requested as treatment of cutaneous wounds since they provide tissue restoration whilst conditioning the delivery of bioactive substances. This paper, developed polymeric blends of chitosan (CH) and polyvinyl alcohol (PVA) containing Triplaris gardneriana ethanolic extract (EEB-Tg). The membranes produced by casting were analyzed by Fourier-transform infrared spectroscopy, thickness, swelling, X-Ray diffraction, mechanical resistance, mucoadhesion, degradation assay, and scanning electron microscopy. The EEB-Tg did not promote significant chemical, morphological, swelling, and crystallinity changes, except in mucoadhesion and mechanical properties. The membrane with EEB-Tg presented an inferior traction resistance (1.41 +/- 1.67 N) and perforation index (7.31 +/- 0.26 N). Regarding bioadhesion force, the same membrane exhibited an inferior mucoadhesion (0.03 +/- 0.003 N). EEB-Tg had little interference in de-gradability but the presence of PVA in the blends influenced these properties. Incorporating bioactive molecules in polymeric curatives can become a groundbreaking measure in the management of wounds and provides an alternative way for skin tissue regeneration.
Currently, phyto-nanotechnology has a crucial impact on the significant changes in agriculture and general plant sciences since it enables target-specific delivery of nanomaterials (NMs) to crops and other plants. Nanotechnology enables the encapsulation of pesticides in NMs to promote their controlled release, increased permeability, stability, and solubility. The slow release of pesticides prevents the rapid degradation of active ingredients from plat sources, which ensures their greater effectiveness. The development of NMs as promising platforms for plant growth, as nanofertilizers and nanopesticides, has gained great attention in recent years. The application of NMs has been considered an alternative solution to control plant pests including insects, fungi, and weeds. NMs can be used as antimicrobial agents in food packing in which several nanoparticles are in intense research. Using nanobiotechnology it also is possible to apply so-called smart plant sensors that can interact with electronic devices and, consequently, allow higher plant productivity. Furthermore, thanks to different NMs, it is possible the translation of plant chemical signals into digital information that can be monitored by properly selected tools. NMs allow the efficient delivery of fertilizers, pesticides, plant growth regulators, and other similar compounds while reducing their consumption and reducing environmental pollution. NMs can also be designed to increase communication between plant roots and the surrounding soil structure.
This chapter aims to provide an overview of the main features that characterize two specific nano-based systems for ocular drug delivery and analyze the main factors that govern their interactions with the ocular surface after topical administration. Nanoemulsion and nanosuspension dosage forms helped to deliver and determine the desired concentration of drugs, improved permeation properties across the corneal and retinal epithelium, decreased the metabolism and clearance preabsorption, and increased the residence time and bioavailability of ophthalmic drugs applied topically, as well as improving patient compliance. As excellent studies have been published previously, the present review will confine itself to the latest research and novel nanomedicine concepts based on nanoemulsions and nanosuspensions, which have been developed for ocular diseases. This chapter focuses on recent developments in nanoemulsion and nanosuspension dosage forms for ocular drug delivery by topical routes. We are outlining the distinct advantages and limitations of nanoemulsions and nanosuspensions and presenting the success achieved by nanomedicines for the treatment of ocular diseases.
Drosophila melanogaster, once considered as a mere fruit-fly, has become a breakthrough model in scientific research since the beginning of the 20th century. Owing to the significant efforts of pioneer scientists in the genetic field, this organism has been fully characterized with respect to its genome, transcriptome, proteome, and metabolome with further developments that are still being achieved. The in-depth knowledge about its morphogenesis, spermatogenesis, and genomic regulation yielded a rigorous and unparalleled opportunity to use this fly-species as a representative toxicological model. Indeed, during the last decades, it has been used in cell polarization studies, autocrine regulation, meiotic divisions as the generation center of a genomic charge compatible with the transmission of life throughout fertilization, and even in the comparison of genomes between populations. This model has been used in several toxicological examinations as it detains important anatomical and physiological features concerning internal structural correlation with the human organism. It also exhibits a fast species turnover, allowing its use in acute and chronic experiments. Owing to its reduced size, Drosophila has also been proposed to screen the toxicological profile of nanomaterials intended for use in higher eukaryotes, including humans. Over the last decades, a new field called drosophotoxicology has emerged, which is expected to expand in the coming years representing an enormous potential for the study of several drugs and nutraceutical compounds from foreign sources, aiming to achieve higher laboratory reproducibility and better quality of outcomes.