RESUMEN
The present study was designed to evaluate whether AuNPs (gold nanoparticles) synthesized with the Cynara scolymus (CS) leaf exert protective and/or alleviative effects on arsenic (As)-induced hippocampal neurotoxicity in mice. Neurotoxicity in mice was developed by orally treating 10â¯mg/kg/day sodium arsenite (NaAsO2) for 21 days. 10⯵g/g AuNPs, 1.6â¯g/kg CS, and 10⯵g/g CS-AuNPs were administered orally simultaneously with 10â¯mg/kg As. CS and CS-AuNPs treatments showed down-regulation of TNF-α and IL-1ß levels. CS and CS-AuNPs also ameliorated apoptosis and reduced the alterations in the expression levels of D1 and D2 dopamine receptors induced by As. Simultaneous treatment with CS and CS-AuNPs improved As-induced learning, memory deficits, and motor coordination in mice assessed by water maze and locomotor tests, respectively. The results of this study provide evidence that CS-AuNPs demonstrated neuroprotective roles with antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as improving D1 and D2 signaling, and eventually reversed neurobehavioral impairments.
Asunto(s)
Arsénico , Cynara scolymus , Nanopartículas del Metal , Extractos Vegetales , Ratones , Animales , Arsénico/metabolismo , Oro , Ratones Endogámicos BALB C , Nanopartículas del Metal/toxicidad , Hipocampo/metabolismoRESUMEN
Hepatocellular carcinoma (HCC), more than 800 000 cases reported annually, is the most common primary liver cancer globally. Doxorubicin hydrochloride (Dox-HCl) is a widely used chemotherapy drug for HCC, but efficacy and tolerability are limited, thus critical to develop delivery systems that can target Dox-HCl to the tumour site. In this study, liver-targeting ligand glycyrrhetinic acid (Gly) was conjugated to polyethylene glycol (PEG) via Steglich reaction and incorporated in liposomes, which were then loaded with Dox-HCl by pH gradient method. The optimal formulation Gly-Peg-Dox-ProLP-F6 showed high Dox-HCl encapsulation capacity (90.0%±1.85%), low particle size (120 ± 3.2 nm). Gly-Peg-Dox-ProLP-F6 formulation demonstrated substantially greater toxicity against HCC cells than commercial Dox-HCl formulation (greater against 1.14, 1.5, 1.24 fold against Hep G2, Mahlavu and Huh-7 cells, respectively), but was 1.86-fold less cytotoxic against non-cancerous cell line AML-12. It increased permeability from apical to basolateral (A-B) approximately 2-fold. Gly-Peg-Dox-ProLP-F6 demonstrated superior antitumor efficacy in mouse liver cancer model as evaluated by IVIS. Isolated mouse liver tissue contained 2.48-fold Dox more than Dox-HCl after administration of Gly-Peg-Dox-ProLP-F6, while accumulation in heart tissue was substantially lower. This Gly-Peg-Dox-ProLP-F6 formulation may improve HCC outcomes through superior liver targeting for enhanced tumour toxicity with lower systemic toxicity.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Ratones , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Polietilenglicoles , Sistemas de Liberación de Medicamentos , Línea Celular TumoralRESUMEN
Sodium hyaluronate (SHA) is an anti-inflammatory and protective agent against bronchoconstriction, and sodium cromoglicate (SCG) prevents exercise-induced bronchoconstriction and inflammation. Based on the pharmacological properties of both substances, this study aimed to develop a dry powder inhaler (DPI) of SHA alone and in combination with SCG. The target of the study was to develop flowable formulations without any surfactants by using the spray drying method. To obtain respirable SHA and SCG:SHA particles, variables of the spray dryer, such as inlet temperature, atomized air flow, and feed solution, were changed. The particles 1-8 µm in size were produced with high yield by spray drying and increasing the ethanol percentage of the feed solution (60%), which is the most remarkable parameter. After that, physicochemical characterizations were performed. The aerosol performance of DPI formulations prepared using lactose was evaluated using Handihaler® DPI. The fine particle fraction (FPF) was 36% for the SHA formulation, whereas it was 52 and 53% for SCG and SHA, respectively, in the SCG:SHA formulation. Consequently, both particles were produced reproducibly by spray drying, and inhaled SHA and SCG:SHA dry powder formulations were developed due to their high FPF and flowability with lactose.