ABSTRACT
Bacterial biofilms are a major health concern, mainly due to their contribution to increased bacterial resistance to well-known antibiotics. The conventional treatment of biofilms represents a challenge, and frequently, eradication is not achieved with long-lasting administration of antibiotics. In this context, the present work proposes an innovative therapeutic approach that is focused on the encapsulation of N-acetyl-l-cysteine (NAC) into lipid nanoparticles (LNPs) functionalized with d-amino acids to target and disrupt bacterial biofilms. The optimized formulations presented a mean hydrodynamic diameter around 200 nm, a low polydispersity index, and a high loading capacity. These formulations were stable under storage conditions up to 6 months. In vitro biocompatibility studies showed a low cytotoxicity effect in fibroblasts and a low hemolytic activity in human red blood cells. Nevertheless, unloaded LNPs showed a higher hemolytic potential than NAC-loaded LNPs, which suggests a safer profile of the latter. The in vitro antibiofilm efficacy of the developed formulations was tested against Staphylococcus epidermidis (Gram-positive) and Pseudomonas aeruginosa (Gram-negative) mature biofilms. The results showed that the NAC-loaded LNPs were ineffective against S. epidermidis biofilms, while a significant reduction of biofilm biomass and bacterial viability in P. aeruginosa biofilms were observed. In a more complex therapeutic approach, the LNPs were further combined with moxifloxacin, revealing a beneficial effect between the LNPs and the antibiotic against P. aeruginosa biofilms. Both alone and in combination with moxifloxacin, unloaded and NAC-loaded LNPs functionalized with d-amino acids showed a great potential to reduce bacterial viability, with no significant differences in the presence or absence of NAC. However, the presence of NAC in NAC-loaded functionalized LNPs shows a safer profile than the unloaded LNPs, which is beneficial for an in vivo application. Overall, the developed formulations present a potential therapeutic approach against P. aeruginosa biofilms, alone or in combination with antibiotics.
Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Drug Carriers/pharmacology , Liposomes/chemistry , Nanoparticles/chemistry , Pseudomonas aeruginosa/drug effects , Acetylcysteine/chemistry , Acetylcysteine/toxicity , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Cell Line , Drug Carriers/chemistry , Drug Carriers/toxicity , Drug Synergism , Humans , Liposomes/toxicity , Mice , Microbial Sensitivity Tests , Moxifloxacin/pharmacology , Nanoparticles/toxicity , Palmitates/chemistry , Palmitates/toxicity , Phosphatidylethanolamines/chemistry , Phosphatidylethanolamines/toxicity , Polyethylene Glycols/chemistry , Polyethylene Glycols/toxicity , Pseudomonas aeruginosa/physiologyABSTRACT
BACKGROUND: Ag2S has the characteristics of conventional quantum dot such as broad excitation spectrum, narrow emission spectrum, long fluorescence lifetime, strong anti-bleaching ability, and other optical properties. Moreover, since its fluorescence emission is located in the NIR-II region, has stronger penetrating ability for tissue. Ag2S quantum dot has strong absorption during the visible and NIR regions, it has good photothermal and photoacoustic response under certain wavelength excitation. RESULTS: 200 nm aqueous probe Ag2S@DSPE-PEG2000-FA (Ag2S@DP-FA) with good dispersibility and stability was prepared by coating hydrophobic Ag2S with the mixture of folic acid (FA) modified DSPE-PEG2000 (DP) and other polymers, it was found the probe had good fluorescent, photoacoustic and photothermal responses, and a low cell cytotoxicity at 50 µg/mL Ag concentration. Blood biochemical analysis, liver enzyme and tissue histopathological test showed that no significant influence was observed on blood and organs within 15 days after injection of the probe. In vivo and in vitro fluorescence and photoacoustic imaging of the probe further demonstrated that the Ag2S@DP-FA probe had good active targeting ability for tumor. In vivo and in vitro photothermal therapy experiments confirmed that the probe also had good ability of killing tumor by photothermal. CONCLUSIONS: Ag2S@DP-FA was a safe, integrated diagnosis and treatment probe with multi-mode imaging, photothermal therapy and active targeting ability, which had a great application prospect in the early diagnosis and treatment of tumor.
Subject(s)
Molecular Probes , Optical Imaging/methods , Photoacoustic Techniques/methods , Quantum Dots , Silver Compounds , A549 Cells , Animals , HeLa Cells , Humans , Hydrophobic and Hydrophilic Interactions , Male , Mice , Mice, Inbred BALB C , Molecular Probes/chemistry , Molecular Probes/toxicity , Phosphatidylethanolamines/chemistry , Phosphatidylethanolamines/toxicity , Phototherapy , Polyethylene Glycols/chemistry , Polyethylene Glycols/toxicity , Quantum Dots/chemistry , Quantum Dots/toxicity , Silver Compounds/chemistry , Silver Compounds/toxicityABSTRACT
El fósforo blanco es un tóxico muy potente empleado en la elaboración de fuegos artificiales, su ingestión accidental o intencional causa un cuadro de intoxicación aguda que evoluciona en cuatro fases clínicas con una alta letalidad. El manejo mediante lavado gástrico con permanganato de potasio o peroxido de hidrogeno, la administración de N-acetyl cisteína y las medidas de soporte, constituyen las bases del tratamiento cuyo éxito depende del inicio precoz. Se presenta el caso de un lactante mayor de 12 meses con ingestión de raspa-raspa, en quien el manejo precoz, ante el riesgo de intoxicación por fósforo blanco, dio como resultado una evolución favorable del paciente.
Subject(s)
Humans , Male , Infant , Phosphatidylethanolamines/poisoning , Phosphatidylethanolamines/toxicity , Phosphorus/adverse effects , Phosphorus/poisoning , Gastric Lavage/methods , Poisoning/etiology , Heart Rate/physiology , Pediatrics , Potassium Permanganate/poisoningABSTRACT
Liposome-encapsulated hemoglobin (LEH) products are being investigated as potential blood substitutes. To determine if changes in LEH composition can modify the immune response, red blood cell substitutes based on conventional lipids containing phosphatidylinositol (LEH1) and sterically stabilized lipid vesicles containing polyethylene glycol phosphatidylethanolamine (LEH2) were tested for effects on host resistance. On Day 0, groups of 18 to 20 female CD-1 mice were given an intravenous (i.v.) infectious challenge with a 20% lethal dose of Listeria monocytogenes. Mice received a single i.v. dose of LEH1, LEH2, or albumin vehicle on Day +1 or Day -3 relative to infectious challenge. Mice dosed with LEH1 and LEH2 on Day +1 died rapidly from Listeria infection; but mice dosed with LEH2 lived significantly longer than did mice receiving LEH1. By contrast, when administered on Day -3, LEH1 had no significant effect on host immunity, while LEH2 increased susceptibility to Listeria infection. In addition, LEH1 and LEH2 both caused significant reduction of phagocytic activity as measured by rat alveolar macrophage (AM) ingestion of latex microspheres. AM incubated 4 hr with either LEH1 or LEH2 prior to addition of microspheres ingested fewer beads in a dose-dependent manner. No difference in in vitro phagocytic activity was observed between LEH1 or LEH2. The inability to differentiate LEH formulations based on in vitro phagocytic activity suggests that the in vivo Listeria infection model may be more relevant in discerning the immunotoxicity of the LEH formulations tested.