RESUMEN
PURPOSE: In general, the surface functionalization of polymeric nanoparticles is carried out by covalently bounding ligands to the nanoparticle surface. This process can cause a lack or decrease of the ligand specificity to its target receptor, besides the need of purification steps. We proposed a ligand-metal-chitosan-lecithin complex as a new strategy to functionalize the surface of biodegradable nanoparticles. METHODS: One pot synthesis of scFv anti-LDL(-)-functionalized nanocapsules was carried out by self-assembly and interfacial reactions. Particle sizing techniques, lipid peroxidation and molecular recognition by enzyme linked immuno sorbent assays were carried out. RESULTS: The selected formulation had unimodal size distribution with mean diameter of about 130 nm. The metals in the complex did not enhance the oxidative stress, and the scFv anti-LDL(-)-functionalized nanocapsules recognized LDL(-) and did not react with native LDL indicating the maintenance of the active site of the fragment. CONCLUSIONS: The one pot synthesis, using the ligand-metal-chitosan-lecithin complex to functionalize the surface of the biodegradable nanocapsules, maintained the active site of the antibody fragment making the device interesting for applications in nanomedicine.
Asunto(s)
Lipoproteínas LDL/inmunología , Nanocápsulas/química , Nanopartículas/química , Polímeros/química , Anticuerpos de Cadena Única/química , Anticuerpos de Cadena Única/inmunología , Dominio Catalítico , Química Farmacéutica/métodos , Quitosano/química , Lecitinas/química , Ligandos , Peroxidación de Lípido/efectos de los fármacos , Metales/química , Estrés Oxidativo/efectos de los fármacos , Tamaño de la PartículaRESUMEN
The hemocompatibility of nanoparticles is of critical importance for their systemic administration as drug delivery systems. Formulations of lipid-core nanocapsules, stabilized with polysorbate 80-lecithin and uncoated or coated with chitosan (LNC and LNC-CS), were prepared and characterized by laser diffraction (D[4,3]: 129 and 134 nm), dynamic light scattering (119 nm and 133 nm), nanoparticle tracking (D50: 124 and 139 nm) and particle mobility (zeta potential: -15.1 mV and +9.3 mV) analysis. In vitro hemocompatibility studies were carried out with mixtures of nanocapsule suspensions in human blood at 2% and 10% (v/v). The prothrombin time showed no significant change independently of the nanocapsule surface potential or its concentration in plasma. Regarding the activated partial thromboplastin time, both suspensions at 2% (v/v) in plasma did not influence the clotting time. Even though suspensions at 10% (v/v) in plasma decreased the clotting times (p<0.05), the values were within the normal range. The ability of plasma to activate the coagulation system was maintained after the addition of the formulations. Suspensions at 2% (v/v) in blood showed no significant hemolysis or platelet aggregation. In conclusion, the lipid-core nanocapsules uncoated or coated with chitosan are hemocompatible representing a potential innovative nanotechnological formulation for intravenous administration.