RESUMO
Amphotericin B (AmB) is a widely used antifungal agent; however, its clinical application is limited due to severe side effects and nephrotoxicity associated with parenteral administration. In recent years, there has been growing interest in the utilization of food-grade materials as innovative components for nanotechnology-based drug delivery systems. This study introduces gliadin/casein nanoparticles encapsulating AmB (AmB_GliCas NPs), synthesized via antisolvent precipitation. Formulation was refined using a 24 factorial design, assessing the influence of gliadin and casein concentrations, as well as organic and aqueous phase volumes, on particle size, polydispersity index (PDI), and zeta potential. The optimal composition with 2 % gliadin, 0.5 % casein, and a 1:5 organic-to-aqueous phase ratio, yielded nanoparticles with a 442 nm size, a 0.307 PDI, a -20 mV zeta potential, and 82 % entrapment efficiency. AmB was confirmed to be amorphous within the nanoparticles by X-ray diffraction. These NPs released AmB sustainably over 96 h, primarily in its monomeric form. Moreover, NPs maintained stability in simulated gastrointestinal fluids with minimal drug release and showed significantly lower hemolytic activity and cytotoxicity on Vero cells than free AmB, suggesting their promise for oral AmB delivery.
Assuntos
Anfotericina B , Nanopartículas , Animais , Chlorocebus aethiops , Anfotericina B/farmacologia , Gliadina , Caseínas , Células Vero , Antifúngicos , Portadores de FármacosRESUMO
Ursolic acid (UA) is a naturally occurring triterpene that has been investigated for its antitumor activity. However, its lipophilic character hinders its oral bioavailability, and therapeutic application. To overcome these limitations, chitosan (CS) modified poly (lactic acid) (PLA) nanoparticles containing UA were developed, characterized, and had their oral bioavailability assessed. The nanoparticles were prepared by emulsion-solvent evaporation technique and presented a mean diameter of 330 nm, zeta potential of +28 mV, spherical shape and 90% encapsulation efficiency. The analysis of XRD and DSC demonstrated that the nanoencapsulation process induced to UA amorphization. The in vitro release assay demonstrated that 53% of UA was released by diffusion after 144 h, following a second-order release kinetics. In simulated gastrointestinal fluids and mucin interaction tests, CS played an important role in stability and mucoadhesiveness improvement of PLA nanoparticles, respectively. In the presence of erythrocytes, nanoparticles proved their hemocompatibility. In tumor cells, nanoparticles presented lower cytotoxicity than free UA, due to slow UA release. After a single oral dose in rats, CS modified PLA nanoparticles increased the UA absorption, reduced its clearance and elimination, resulting in increased bioavailability. The results show the potential application of these nanoparticles for UA oral delivery for cancer therapy.
Assuntos
Quitosana/química , Nanopartículas/química , Poliésteres/química , Triterpenos/química , Triterpenos/metabolismo , Animais , Disponibilidade Biológica , Linhagem Celular Tumoral , Emulsões/química , Eritrócitos/efeitos dos fármacos , Humanos , Masculino , Ratos , Ratos Wistar , Solventes/química , Ácido UrsólicoRESUMO
The objective of this study was to develop zein-casein-lysine nanoparticles to modulate the intestinal permeability of ferulic acid (FA), a bioactive compound with proven antioxidant properties. The nanoparticles were obtained by a liquid-liquid dispersion method and were characterized in terms of mean size, polydispersity index, zeta potential, association efficiency (AE), in vitro drug release, x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The in vitro intestinal permeability of nanoparticles was evaluated through Caco-2 and Caco-2/HT29-MTX monoculture and co-culture models, respectively. Nanoparticles presented a mean size of 199â¯nm and zeta potential of -26â¯mV. The AE of FA was 23% evaluated by high-performance liquid chromatography (HPLC). XRD showed amorphization of FA after association and FT-IR showed no changes in chemical structures of the compounds after nanoencapsulation. The cytotoxicity assays demonstrated that multicomposite nanoparticles presented a safe profile against Caco-2 and HT29-MTX cells. In the in vitro permeability assay, free FA exhibited higher permeability compared to FA-loaded nanoparticles, possibly due to prolonged FA release from nanoparticles. These new developed zein-casein-lysine nanoparticles may be used for FA sustained delivery by the oral route.
Assuntos
Caseínas/química , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Mucosa Intestinal/metabolismo , Lisina/química , Nanopartículas/química , Zeína/química , Administração Oral , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Ácidos Cumáricos/administração & dosagem , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacosRESUMO
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive and incapacitating decay of cognitive, neuropsychiatric, and behavioral manifestations. L-tryptophan is the precursor amino acid of serotonin, which is a neurotransmitter responsible for mood balance and the sense of well-being and can be administered in the form of nanoparticles. OBJECTIVE: This study analyzed the effectiveness of L-tryptophan nanoparticles and L-tryptophan on behavioral physiological alterations resulting from AD in animal models. METHODS: The sample consisted of 50 Rattus norvegicus rats, divided in 10 groups with 5 animals each: one negative control (NC), three positive control groups (C3, C7, and C21), three groups treated with L-tryptophan nanoparticles (T3N, T7N, and T21N) at the concentration of 1.5 mg, and three groups treated with L-tryptophan (T3L, T7L, and T21L) at the concentration of 1.5 mg. The rats underwent stereotactic surgery to induce AD through the injection of amyloid beta-amyloid peptide1-42 in the intracerebroventricular region. All rats were submitted to pre- and post-surgery and post-treatment motor behavior evaluation through the Later Water Maze (LWM) and elevated cross-labyrinth (ECL). Histological analysis was performed to verify the presence of senile plaques, and the statistical analysis used the unpaired T-test. RESULTS: Significant intergroup differences were observed in some of the evaluated parameters between treated and untreated groups. CONCLUSION: It was concluded that the treatment with L-tryptophan nanoparticles was beneficial to improve behavioral reactions in the Alzheimer's model.
Assuntos
Doença de Alzheimer/prevenção & controle , Comportamento Animal/efeitos dos fármacos , Triptofano/farmacologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/administração & dosagem , Animais , Infusões Intraventriculares , Nanopartículas/química , Fragmentos de Peptídeos/administração & dosagem , Placa Amiloide/patologia , Ratos , Triptofano/químicaRESUMO
Amphotericin B (AmB) is a broad-spectrum antifungal drug used in the treatment of fungal invasive infections. However, its clinical use has been limited due to its side effects and toxicity, especially the nephrotoxicity. Furthermore, AmB presents low aqueous solubility, low permeability over the membranes and poor stability in the gastric environment, which makes it unavailable to be administered by the oral route. In this study, chitosan-coated poly (ε-caprolactone) nanoparticles were developed to provide the oral delivery of AmB and reduce its toxicity. Nanoparticles were obtained by nanoprecipitation and parameters as particle size, polydispersity index (PDI), zeta potential, morphology, in vitro AmB release (in physiological pH and simulated gastrointestinal fluids), state of molecular aggregation, cytotoxicity over erythrocytes and Vero cells line and in vitro antifungal activity were fully investigated. Nanoparticles presented mean size of 318 ± 35 nm, PDI of 0.24 ± 0.02, zeta potential of +36.2 ± 1.8 mV due to chitosan-coating, and 69% of AmB encapsulation. The kinetic release profile of AmB from nanoparticles was of second order and diffusion-governed in pH 7.4. The release in the gastrointestinal simulated fluids showed that the chitosan-coated PCL nanoparticles presented good stability during the time evaluated. AmB was released from nanoparticles in a state of low molecular aggregation. Cytotoxicity over erythrocytes and Vero cells line revealed that nanoencapsulation significantly reduced the AmB-related cytotoxicity (p < 0.05) compared to the free drug. In the antifungal activity against Candida parapsilosis strain, the MIC of AmB-loaded nanoparticles was 5-fold higher than free AmB, but the strain was susceptible to nanostructured AmB. Chitosan-functionalized PCL are potential carriers for the oral AmB delivery, reducing its cytotoxicity and maintaining its activity.