ABSTRACT
This study reports on the successful use of magnetic albumin nanosphere (MAN), consisting of maghemite nanoparticles hosted by albumin-based nanosphere, to target different sites within the central nervous system (CNS). Ultrastructural analysis by transmission electron microscopy (TEM) of the material collected from the mice was performed in the time window of 30 minutes up to 30 days after administration. Evidence found that the administered MAN was initially internalized and transported by erythrocytes across the blood-brain-barrier and transferred to glial cells and neuropils before internalization by neurons, mainly in the cerebellum. We hypothesize that the efficiency of MAN in crossing the BBB with no pathological alterations is due to the synergistic effect of its two main components, the iron-based nanosized particles and the hosting albumin-based nanospheres. We found that the MAN in targeting the CNS represents an important step towards the design of nanosized materials for clinical and diagnostic applications.
Subject(s)
Central Nervous System Agents/chemistry , Magnetite Nanoparticles/chemistry , Nanocomposites/chemistry , Serum Albumin, Bovine/chemistry , Animals , Blood Cells/chemistry , Blood Cells/cytology , Brain/cytology , Brain/metabolism , Brain/ultrastructure , Brain Chemistry , Cattle , Central Nervous System Agents/administration & dosage , Central Nervous System Agents/pharmacokinetics , Drug Delivery Systems/methods , Histocytochemistry , Magnetite Nanoparticles/administration & dosage , Mice , Microscopy, Electron, Transmission , Nanocomposites/administration & dosage , Particle Size , Serum Albumin, Bovine/administration & dosage , Serum Albumin, Bovine/pharmacokinetics , Tissue DistributionABSTRACT
BACKGROUND: The magnetic albumin nanosphere (MAN), encapsulating maghemite nanoparticles, was designed as a magnetic drug delivery system (MDDS) able to perform a variety of biomedical applications. It is noteworthy that MAN was efficient in treating Ehrlich's tumors by the magnetohyperthermia procedure. METHODS AND MATERIALS: In this study, several nanotoxicity tests were systematically carried out in mice from 30 minutes until 30 days after MAN injection to investigate their biocompatibility status. Cytometry analysis, viability tests, micronucleus assay, and histological analysis were performed. RESULTS: Cytometry analysis and viability tests revealed MAN promotes only slight and temporary alterations in the frequency of both leukocyte populations and viable peritoneal cells, respectively. Micronucleus assay showed absolutely no genotoxicity or cytotoxicity effects and histological analysis showed no alterations or even nanoparticle clusters in several investigated organs but, interestingly, revealed the presence of MAN clusters in the central nervous system (CNS). CONCLUSION: The results showed that MAN has desirable in vivo biocompatibility, presenting potential for use as a MDDS, especially in CNS disease therapy.
Subject(s)
Biocompatible Materials/toxicity , Drug Delivery Systems/methods , Magnetite Nanoparticles/toxicity , Serum Albumin, Bovine/toxicity , Analysis of Variance , Animals , Brain Chemistry/drug effects , Cell Survival/drug effects , Female , Flow Cytometry , Histocytochemistry , Leukocyte Count , Leukocytes/drug effects , Materials Testing , Mice , Micronucleus Tests , Nanospheres/toxicity , Toxicity TestsABSTRACT
Six novel peptides called phylloseptins (PS-1, -2, -3, -4, -5, and -6) showing anti-bacterial (PS-1) and anti-protozoan (PS-4 and -5) activities were isolated from the skin secretion of the Brazilian tree-frogs, Phyllomedusa hypochondrialis and Phyllomedusa oreades. Phylloseptins have a primary structure consisting of 19-21 amino acid residues (1.7-2.1 kDa). They have common structural features, such as a highly conserved N-terminal region and C-terminal amidation. Phylloseptin-1 (FLSLIPHAINAVSAIAKHN-NH2) demonstrated a strong effect against gram-positive and gram-negative bacteria (MICs ranging from 3 to 7.9 microM), without showing significant hemolytic activity (<0.6% at the MIC range) towards mammalian cells. Atomic force microscopy experiments indicated that the bacteriolytic properties of these peptides might be related to their disruptive action on the cell membrane, characterized by a number of bubble-like formations, preceding every cell lysis. PS-4 and PS-5 showed anti-protozoan activity with IC50 at about 5 microM for Trypanosoma cruzi.
