Dextran (Dex), polysialic acid (PSA), hyaluronic acid (HA), chitosan (CH), and heparin are the most used natural polysaccharides. Synthetic polymers

include polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), polyacrylamide (Pam), poly(ethylene glycol) (PEG), and PEG-based copolymers such as poloxamers, poloxamines, and polysorbates. 2.2.1. PEG Poly(ethylene glycol) (PEG) is the polymer of choice to produce stealth nanocarriers. This neutral, flexible, and hydrophilic material Inhibitors,research,lifescience,medical can in fact properly produce surface barrier layers that reduce the adhesion of opsonins present in the blood serum on the nanoparticles making them “DAPT secretase DAPT Inhibitor invisible” to phagocytic cells. The protein repulsion operated by PEG was also visualized by freeze-fracture transmission

electron microscopy (TEM) [29]. A few physical protocols have been adopted to coat nanoparticle with PEG [22], even though these procedures entail the risk of polymer desorption in the blood with Inhibitors,research,lifescience,medical consequent loss of the beneficial contribution of the polymer [30]. In order to overcome this problem, covalent PEG conjugation protocols have been developed [31, 32]. Biodegradable nanoparticles with PEG covalently bound to the surface have been produced using PEG derivatives of poly(lactic Inhibitors,research,lifescience,medical acid), poly(lactic acid-co-glycolic acid) [33], or poly(alkylcyanoacrylates) [34]. The nanoparticles are prepared by emulsion, precipitation, or dispersion protocols in aqueous media. These procedures allow for the PEG orientation toward Inhibitors,research,lifescience,medical the water phase, while the biodegradable hydrophobic polymer fraction is physically entangled in the inner nanoparticle matrix [22]. Alternatively, PEG chains may be covalently conjugated to preformed nanoparticles through surface functional groups [35, 36]. 2.2.2. Poloxamine and Poloxamer Poloxamines (Tetronics) Inhibitors,research,lifescience,medical and poloxamers (Pluronics) are amphiphilic block copolymers consisting of hydrophilic blocks of ethylene

oxide (EO) and hydrophobic blocks of propylene oxide (PO) monomer units. Cilengitide Poloxamers are a-b-a type triblock copolymers (PEO-PPO-PEO) while poloxamines are tetrablock copolymers of PEO-PPO connected through ethylenediamine bridges [(PEO-PPO)2–N–CH2–CH2–N–(PPO-PEO)2] [37–39]. These polymers can be physically adsorbed on the nanocarrier surface through the hydrophobic PPO fraction [22]. Following intravenous injection to mice and rats, poloxamer- or poloxamine-coated sub-200nm poly(phosphazene) [40], PLGA nanoparticles [41], and liposomes [42, 43] did not show prolonged circulation time as compared to the uncoated counterparts. This unexpected behaviour was ascribed to the desorption of the polymers from the nanocarrier surface [30] as well as to the polymer capacity to adsorb opsonins [44].