These methods have been

translated to obtain stealth nanoparticles with other materials [152, 153]. 2.6.1. Physical Coating of Polymeric Nanoparticles and Liposomes Surface PEG coating of PLGA nanoparticles was carried out using 2kDa PEG-DSPE as emulsifier during oil-in-water microRG7422 mouse emulsion nanoparticle preparation. The process allows for the embedding of the PEG-DSPE phospholipid fraction in the PLGA matrix by hydrophobic interactions, whereas the hydrophilic PEG chain extends outward the nanoparticle surface, forming a polymeric brush that stabilizes the system. Drug loaded 120nm PEGylated PLGA nanoparticles were successfully used for the treatment of a cystic fibrosis murine model by intranasal administration [154]. An original Inhibitors,research,lifescience,medical multistep technique for physical Inhibitors,research,lifescience,medical PEGylation of doxorubicin

loaded PLGA nanoparticles involves the surface adsorption of palmitate-avidin on the particles through the avidin alkyl chain anchor during the particle preparation by emulsion. The avidinated particles are subsequently PEGylated by exposure to PEG-biotin. The particle coating with 5 and 10kDa PEG reduced protein adsorption by 50, and 75%, respectively, compared to the non-PEGylated PLGA nanoparticles. Approximately Inhibitors,research,lifescience,medical 3% of the initial dose of the doxorubicin loaded nanoparticles intravenously administered was detected in the serum after 48 hours from administration. This corresponds to a twofold residual doxorubicin plasma concentration as compared to that obtained with non-PEGylated

particles [155]. Protective PEG layer on liposomes can be achieved through two very conventional strategies. In the first approach PEG is conjugated with a hydrophobic moiety (usually the residue of PE or a long chain fatty acid is reacted with methoxy-PEG-hydroxysuccinimide ester) [156, 157] (Figure 4). Subsequently Inhibitors,research,lifescience,medical a dry mixture film of phospholipids and the mPEG-PE is rehydrated to yield liposomes Inhibitors,research,lifescience,medical that spontaneously expose the PEG chains on their surface [158]. Figure 4 Structures of PEG-lipid conjugates used in preparing stealth liposomes. The derivative is obtained with a PEG chain of 45 monomers, corresponding to a molecular weight of approximately 2000Da. PEG units are capped at the distal also end with a methoxy … A second approach to coat liposomes with PEG is called the “postinsertion method” and consists in the conjugation of activated PEG to preformed liposomes. 2.6.2. Polymer Coating of Magnetic Iron Oxide Nanoparticles Specific coating protocols have been set up to produce stealth inorganic nanoparticles. The incorporation of a polymer coating on the nanoparticle surface can be achieved either via “one-pot” methods, where the nanoparticles are coated by a polymer dissolved in the particle production mixture, or by “two-step” or “postproduction” method, where nanoparticles are first generated and then coated with a polymer. Magnetic nanoparticles coated with PEG-based copolymers have been prepared in one pot by Fe3O4 nucleation and growth.