, 2010a,b) However, hydrophilic core–shell nanostructures were p

, 2010a,b). However, hydrophilic core–shell nanostructures were phagocytosed by endosomal route. Therefore, we modified the hydrophilic core–shell nanostructures by incorporating amphiphilic copolymers into the shells to render them selleck chemical more hydrophobic. Gentamicin encapsulation in core–shell nanostructures that contained some poly(propylene oxide) with an average block length of 68 repeat units in the shells in addition to the hydrophilic polyethylene oxide block enhanced the rate and modulated the route of cell uptake by augmenting nonendosomal uptake (Ranjan et al., 2009a ,b). The stabilities of those nanostructures in the presence of phosphate salts, however, were relatively poor. Thus, to improve

the stabilities of the core–shell nanostructures at the physiological pH of 7.4, 37 °C, and 0.1 M NaCl, we incorporated a higher molecular LY2157299 mouse weight hydrophobic poly(propylene oxide) with an average of 85 repeat units in the shells, and also more poly(propylene oxide) relative to the hydrophilic polyethylene oxide (Fig. 2). This enhanced hydrophobic interactions contributed to nanostructure stabilities

in physiological media in addition to its nonendosomal uptake. It is also critical that physicochemical characteristics of the nanocarriers like size, zeta potential, pH sensitivity, and surface chemistry are controlled carefully. For example, nanocarriers with a low-positive zeta potential and diameter > 80 nm are rapidly taken up by reticuloendothelial cells (Rudt, 1993). Uptake by macrophages of quantum dot containing anionic carboxylates is more rapid compared with amino-functional polyethylene oxide (Clift et al., 2008). Likewise, the phagocytosis of hydrophilic core–shell nanostructures modified with polyethylene glycol is less

efficient by the polymorphonuclear cells (Zahr et al., 2006). In general, Resminostat preliminary results from our and other studies show that the presence of hydrophobic functional groups on the polymeric surface has a stimulatory effect both in adhesion and internalization by the cells (Mainardes et al., Ranjan et al., 2009; 2010a ,b). Thus, we hypothesize that nanocarrier uptake is correlated with particle surface chemistry and should be a subject of further investigation. Antimicrobials encapsulated nanocarriers have been tested in vitro and in vivo against salmonellosis. In vitro treatment using ampicillin-loaded polycyanoacrylate nanocarriers shows marked destruction of the intracellular Salmonella in peritoneal cells and J774A.1 murine macrophage cells (Pinto-Alphandary et al., 1994; Balland et al., 1996). The killing action of the ampicillin nanocarriers was attributed to cell wall destruction of the Salmonella, shown by the presence of numerous spherical bodies in the cell cytoplasm. Also, the actions of these nanocarriers were time dependent. For example, intracellular Salmonella clearance upon a 12-h treatment produced significant differences compared with free ampicillin.

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