RESUMO
Despite the promising potential of Solanum plant glycoalkaloids in combating skin cancer, their clinical trials have been halted due to dose-dependent toxicity and poor water solubility. In this study, we present a rational approach to address these limitations and ensure colloidal stability of the nanoformulation over time by designing solid lipid-polymer hybrid nanoparticles (SLPH). Leveraging the biocompatible and cationic properties of polyaspartamides, we employed a new polyaspartamide derivative (P1) as a raw material for this class of nanostructures. Subsequently, we prepared SLPH through a one-step process involving hot-melt emulsification followed by ultrasonication. The physicochemical properties of the SLPH were thoroughly characterized using dynamic light scattering (DLS), ζ-potential analysis, nanoparticle tracking analysis (NTA), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). The optimized formulation exhibited long-term stability over six months under low temperatures, maintaining a particle size around 200â¯nm, a polydispersity index (PdI) lower than 0.2, and a ζ-potential between +35-40â¯mV. Furthermore, we evaluated the cytotoxic effect of the SLPH against human cutaneous melanoma cells (SK-MEL-28) compared to human foreskin fibroblast cells (HFF-1). Encapsulation of glycoalkaloids into the nanoparticles (SLPH-GE) resulted in a two-fold greater selective cytotoxic profile for melanoma cells than glycoalkaloids-free (GE). The nanoparticles disrupted the stratum corneum barrier with a penetration depth of approximately 77 µm. These findings underscore the potential of the developed nanosystem as an effective glycoalkaloid carrier with suitable colloidal and biological properties for further studies in topical treatment strategies for cutaneous melanoma.
Assuntos
Lipídeos , Melanoma , Nanopartículas , Polímeros , Humanos , Nanopartículas/química , Lipídeos/química , Melanoma/tratamento farmacológico , Melanoma/patologia , Polímeros/química , Polímeros/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Tamanho da Partícula , Alcaloides/química , Alcaloides/farmacologia , Linhagem Celular Tumoral , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Administração Tópica , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Propriedades de SuperfícieRESUMO
The therapeutic potential of medicinal plants is known as an alternative in treatment of human affections; in effect, the conventional application of these medicinal sources has several limitations like low bioavailability, solubility and stability, which affect its pharmacological efficacy. In recent decades, extraordinary advances have been made in new drug delivery systems using nanocarriers. This work consisted in determining the in vitro antifungal activity of the methanolic extract of Euphorbia tirucalli formulated in polymeric nanoparticles. The antifungal activity was determined by the microdilution method in 96-well microplates, applying nanoparticles loaded with plant extract (NP-Ext) obtained by nanoprecipitation on clinical isolates of Trichophyton rubrum and T. interdigitalis. Regarding the nanoparticles, the lots used did not present significant differences in their physicochemical characteristics, with a size of 91.885 ± 1.621nm, polydispersity index of 0.152 ± 0.025 and Z-potential of -6.047 ± 0.987. The quantification of the extract in the polymeric matrix was determined by infrared spectroscopy (FTIR), where an efficiency and encapsulation percentage of 22.15 ± 0.82 and 2.95 ± 0.11, respectively, were obtained. The in vitro antifungal activity of the crude and formulated extract was obtained calculating the Minimum Inhibitory Concentration (MIC) of each one; a MIC of 125 µg/mL was obtained against T. rubrum and T. interdigitalis with the crude extract, while a MIC value of 55.55 and 0.1 µg/mL was obtained with NP-Ext, respectively, against these same. Conclusions: biological activity is closely linked to the phytochemical profile of the extract; while the improvement of said potential with the NP-Ext with the dosage form was directly related to the physicochemical characteristics of the nanocarrier.
Assuntos
Antifúngicos , Euphorbia , Testes de Sensibilidade Microbiana , Nanopartículas , Extratos Vegetais , Euphorbia/química , Antifúngicos/farmacologia , Antifúngicos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Nanopartículas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Trichophyton/efeitos dos fármacos , Polímeros/farmacologia , Polímeros/química , ArthrodermataceaeRESUMO
The design, development, and obtaining of nanostructured materials, such as polymeric nanoparticles, have garnered interest due to loading therapeutic agents and its broad applicability. Polymeric nanoparticle synthesis employs advanced techniques such as the double emulsion approach and the pH-driven method, allowing the efficient incorporation of active compounds into these matrices. These loading methods ensure compound stability within the polymeric structure and enable control of the release of therapeutic agents. The ability of loaded polymeric nanoparticles to transport and release therapeutic agents on target manner represents a significant advancement in the quest for effective therapeutic solutions. Amid escalating concerns regarding antimicrobial resistance, interventions using polymeric nanostructures stand out for the possibility of carrying antimicrobial agents and enhancing antibacterial action against antibiotic-resistant bacteria, making a new therapeutic approach or complement to conventional treatments. In this sense, the capability of these polymeric nanoparticles to act against Escherichia coli underscores their relevance in controlling bacterial infections. This mini-review provides a comprehensive synthesis of promising techniques for loading therapeutic agents into polymeric nanoparticles highlighting methodologies and their implications, addressing prospects of combating bacterial infections caused by E. coli. KEY POINTS: ⢠The double emulsion method provides control over size and release of bioactives. ⢠The pH-driven method improves the solubility, stability, and release of active. ⢠The methods increase the antibacterial action of those encapsulated in PNPs.
Assuntos
Antibacterianos , Emulsões , Infecções por Escherichia coli , Escherichia coli , Nanopartículas , Polímeros , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Concentração de Íons de Hidrogênio , Emulsões/química , Polímeros/química , Polímeros/farmacologia , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Produtos Biológicos/química , Produtos Biológicos/farmacologiaRESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment associated with the accumulation of beta-amyloid protein (Aß). Aß activates glial cells in the brain, increasing the secretion of proinflammatory cytokines, which leads to neuroinflammation and neuronal death. Currently, there are no effective treatments that cure or stop its progression; therefore, AD is considered a global health priority. The main limitations are the low drug bioavailability and impermeability of the blood-brain barrier (BBB). Fortunately, nanomedicine has emerged as a promising field for the development of new nanosystems for the controlled and targeted delivery of drugs to the brain. Therefore, in this work, lipid-polymer hybrid nanoparticles (LPHNPs) conjugated with transferrin (Tf) to facilitate crossing the BBB and loaded with N-acetylcysteine (NAC) for its anti-inflammatory effect were synthesized, and their physicochemical characterization was carried out. Subsequently, an in vitro model involving human astrocytes derived from induced pluripotent stem cells (iPSC) from an AD-diagnosed patient was developed, which was brought to a reactive state by stimulation with lipopolysaccharides (LPSs). The cell culture was treated with either Tf-conjugated LPHNPs loaded with NAC (NAC-Tf-LPHNPs) at 0.25 mg mL-1, or free NAC at 5 mM. The results showed that NAC-Tf-LPHNPs favorably modulated the expression of proinflammatory genes such as interleukin-1ß (IL-1ß), amyloid precursor protein (APP) and glial fibrillary acidic protein (GFAP). In addition, they reduced the secretion of the proinflammatory cytokines interleukin 6 (IL-6), IL-1ß and interferon-gamma (INF-γ). Results for both cases were compared to the group of cells that did not receive any treatment. In contrast, free NAC only had this effect on the expression of IL-1ß and the secretion of the cytokines IL-6 and INF-γ. These results indicate the potential of NAC-Tf-LPHNPs for AD treatment.
Assuntos
Acetilcisteína , Doença de Alzheimer , Astrócitos , Células-Tronco Pluripotentes Induzidas , Nanopartículas , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Nanopartículas/química , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Acetilcisteína/química , Acetilcisteína/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Polímeros/química , Polímeros/farmacologia , Lipídeos/química , Biomarcadores/metabolismo , Tamanho da Partícula , Doenças Neuroinflamatórias/tratamento farmacológicoRESUMO
Some synthetic polymers can be used at low concentrations to reduce the toxicity of conventional cryoprotectant agents. In this study we investigated whether the addition of synthetic polymers to a conventional cryoprotectant solution would improve the cryopreservation of bovine ovarian tissue. Freshly collected ovaries from ten adult crossbred cows were incised using a scalpel in the frontal section. From each cow, ovarian cortical slices of 1 mm thickness were divided into 30 fragments of 3 × 3 mm, of which 10 served as fresh controls, 10 were vitrified with conventional cryoprotectant agents (2.93 M glycerol, 27 % w/v; 4.35 M ethylene glycol, 27 % w/v), and 10 were vitrified using the same cryoprotectant agents in addition to synthetic polymers (0.2 % PVP K-12, 0.2 % SuperCool X-1000 ™ w/v and 0.4 % SuperCool Z-1000 ™ w/v). After warming, histology was used to assess follicular quantity and integrity, while in vitro culture of mechanically isolated follicles encapsulated in an alginate matrix was performed for 15 days to assess their growth and hormonal production. Vitrified ovarian tissues presented abnormal morphology, a higher percentage of atretic follicles, and their isolated follicles had lower survival rates and lower frequency of antrum formation during in vitro culture compared to those from fresh tissue. At the end of culture, the follicles that had been cryopreserved produced less estradiol and progesterone than the fresh ones. The addition of synthetic polymers during tissue vitrification did not modify any of these parameters. We conclude that, under the conditions of this study, the use of this combination of synthetic polymers for tissue vitrification did not enhance the preservation of the morphological or functional integrity of bovine ovarian follicles.
Assuntos
Criopreservação , Crioprotetores , Etilenoglicol , Glicerol , Folículo Ovariano , Ovário , Vitrificação , Animais , Feminino , Bovinos , Crioprotetores/farmacologia , Criopreservação/métodos , Criopreservação/veterinária , Ovário/efeitos dos fármacos , Glicerol/farmacologia , Etilenoglicol/farmacologia , Folículo Ovariano/efeitos dos fármacos , Polímeros/farmacologia , Polímeros/química , Progesterona/farmacologia , Estradiol/farmacologia , Alginatos/química , Alginatos/farmacologiaRESUMO
AIMS: The purpose was to evaluate the antimicrobial activity of highly soluble polypyrrole (Hs-PPy), alone or combined with oxacillin, as well as its antibiofilm potential against methicillin-resistant Staphylococcus aureus strains. Furthermore, the in silico inhibitory mechanism in efflux pumps was also investigated. METHODS AND RESULTS: Ten clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and two reference strains were used. Antimicrobial activity was determined by broth microdilution, and the combination effect with oxacillin was evaluated by the checkerboard assay. The biofilm formation capacity of MRSA and the interference of Hs-PPy were evaluated. The inhibitory action of Hs-PPy on the efflux pump was evaluated in silico through molecular docking. Hs-PPy showed activity against the isolates, with inhibitory action between 62.5 and 125 µg ml-1 and bactericidal action at 62.5 µg ml-1, as well as synergism in association with oxacillin. The isolates ranged from moderate to strong biofilm producers, and Hs-PPy interfered with the formation of this structure, but not with mature biofilm. There was no in silico interaction with the efflux protein EmrD, the closest homolog to NorA. CONCLUSIONS: Hs-PPy interferes with biofilm formation by MRSA, has synergistic potential, and is an efflux pump inhibitor.
Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Polímeros/farmacologia , Pirróis/farmacologia , Simulação de Acoplamento Molecular , Oxacilina/farmacologia , Anti-Infecciosos/farmacologia , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
Plastination consists of replacing lipid and water with a curable polymer. This technique has numerous advantages, of which the production of non-toxic, inert, highly durable, dry, and easy maintenance and storage specimens stand out. Like all anatomical techniques, plastination also has disadvantages, and one of them is tissue shrinkage. The feasibility of using low viscosity domestic silicone (0,1Pa.s at 20°C) to plastinate brain slices was examined. Twenty humans, 10 millimeters (mm) brain slices were impregnated, ten slices each with two polymers [10 with domestic low viscosity polymer - P1 and 10 slices with Biodur® (0,45-0,6Pa.s at 20°C) S10]. Shrinkage was accessed by volume and area measurements. Volume shrinkage was significantly less in the slices impregnated with low viscosity domestic polymer, demonstrating the feasibility to plastinate brain slices with domestic low viscosity silicone polymer.
Assuntos
Plastinação , Silicones , Humanos , Viscosidade , Polímeros/farmacologia , Plastinação/métodos , EncéfaloRESUMO
Silver nanoparticles incorporation into polymeric packaging aims to prevent microbiological contamination in food products, thus ensuring superior food safety and preservation. In this context, this study aimed to verify the antimicrobial efficacy of linear low-density polyethylene (LLDPE) films incorporated with silver nanoparticles (AgNPs) dispersed in silica (SiO2) and hydroxyapatite (HAP) carriers at different concentrations. AgNPs + carriers polymer films were characterized at 0.2, 0.4, and 0.6% concentrations using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), field emission gun-scanning electron microscope (FEG-SEM), thermogravimetric analyzer (TGA), differential scanning calorimetry (DSC), and migration in acidic and non-acidic simulants. Antimicrobial action was investigated on Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and the Penicillium expansum and Fusarium solani fungi with antimicrobial activity by direct contact test and bacterial imaging by scanning electron microscopy. AgNPs addition to the LLDPE matrix did not interfere with the films' chemical and thermal properties and presented no significant migration to the external medium. For antimicrobial action, silver nanoparticles showed, in most concentrations, an inhibition percentage higher than 90% on all microorganisms studied, regardless of the carrier. However, a greater inhibitory action on S. aureus and between carriers was found, making hydroxyapatite more effective. The results indicated that nanostructured films with AgNPs + hydroxyapatite showed more promising antimicrobial action on microorganisms than AgNPs + silica, making hydroxyapatite with silver nanoparticle potentially useful in food packaging, improving safety and maintaining quality.
Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Antibacterianos/farmacologia , Antibacterianos/química , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Polietileno/química , Polietileno/farmacologia , Dióxido de Silício/farmacologia , Embalagem de Alimentos , Staphylococcus aureus , Durapatita/farmacologia , Anti-Infecciosos/farmacologia , Polímeros/farmacologia , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The design of hydrogels based on natural polymers that have modulation of antibacterial capacity, ideal performance in release capacity of encapsulated drugs, and desired bioactivity for applications in wound healing represents a modern trend in biomaterials. In this work, novel hydrogels of semi-interpenetrating polymeric networks based on collagen and xanthan gum (XG) were investigated. The linear chains of XG can semi-interpenetrate inside to matrix of crosslinked collagen with polyurethane under physiological conditions, generating amorphous surfaces with fibrillar-granular reliefs that have accelerated gelation time (about 15 min), super water absorption (up to 3100%) and high inhibition capacity of pathogenic bacteria such asEscherichia coli(up to 100% compared to amoxicillin at 20 ppm). The increment of XG in the hydrogel (up to 20 wt.%) allows for improvement in the storage module, resistance to thermal degradation, slow the rate of hydrolytic and proteolytic degradation, allowing to encapsulate and controlled release of molecules such as ketorolac and methylene blue; besides, it shows to keep the metabolic activity of fibroblasts and monocytes at 48 h of evaluation, without observing cytotoxic effects. The bioactivity of these hydrogels is improved since they have excellent hemocompatibility and enhanced cell proliferation. Specifically, the hydrogel with 20 wt.% of XG shows to decrease the production of tumor necrosis factor-αand CCL-2 cytokines, increasing the production of transforming growth factor-ßin human monocytes, which could be used to modulate inflammation and regenerative capacity in wound healing strategies.
Assuntos
Colágeno , Hidrogéis , Humanos , Liberação Controlada de Fármacos , Hidrogéis/farmacologia , Colágeno/farmacologia , Cicatrização , Polímeros/farmacologia , Antibacterianos/farmacologiaRESUMO
Polypyrrole (PPy) is one of the most studied conductive polymers due to its electrical conductivity and biological properties, which drive the possibility of numerous applications in the biomedical area. The physical-chemical features of PPy allow the manufacture of biocompatible devices, enhancing cell adhesion and proliferation. Furthermore, owing to the electrostatic interactions between the negatively charged bacterial cell wall and the positive charges in the polymer structure, PPy films can perform an effective antimicrobial activity. PPy is also frequently associated with biocompatible agents and antimicrobial compounds to improve the biological response. Thus, this comprehensive review appraised the available evidence regarding the PPy-based films deposited on metallic implanted devices for biomedical applications. We focus on understanding key concepts that could influence PPy attributes regarding antimicrobial effect and cell behavior under in vitro and in vivo settings. Furthermore, we unravel the several agents incorporated into the PPy film and strategies to improve its functionality. Our findings suggest that incorporating other elements into the PPy films, such as antimicrobial agents, biomolecules, and other biocompatible polymers, may improve the biological responses. Overall, the basic properties of PPy, when combined with other composites, electrostimulation techniques, or surface treatment methods, offer great potential in biocompatibility and/or antimicrobial activities. However, challenges in synthesis standardization and potential limitations such as low adhesion and mechanical strength of the film must be overcome to improve and broaden the application of PPy film in biomedical devices.