2). Pratten and Llyod [30] have described that for a particle size of 30 nm, uptake would occur through pinocytosis where as in case of drug particles more than 100 nm, the process occurs through phagocytosis. Moreover, particle size greater than 300 nm and beyond stealth properties are minimal even in case of appropriate coating of

drug [31]. Accordingly, formulations F3–F5 failed to show good efficacy in the systemic infectious models (data not shown) even though, these formulations exhibiting required feature like osmolarity, which is more physiological to mouse blood and tissue. From Forskolin chemical structure these observations without any ambiguity it is clear that T-80 has a concentration dependent influence leading to changes in pharmacokinetics of the drug candidate [32] and [33]. Formulations F6–F8 demonstrated higher plasma exposure values (AUClast averaged above 13.0 µg h mL−1

and C0 averaged above 80 µg h mL−1) are shown in Fig. 5a and GW-572016 datasheet b and the corresponding pharmacokinetic parameter values in Table 2. They also exhibited very effective in vivo efficacy against MRSA and VRE. In the BALB/c murine septicemia model one of these formulations (F6) shown osmolarity value close to the mouse blood, displayed an ED100 value of 2.5 mg kg−1 against MRSA and 10.0 mg kg−1 against VRE [5]. It was reported that, to

avoid the rapid clearance of nanoparticles from the blood, it is important to block the initial process of opsonization. PEGylation is one of the widely used Glutathione peroxidase strategies to prepare stealth particles that minimize or avoid opsonization. PEGylation refers to adsorption, grafting, or covalent attachment of hydrophilic PEG chains on the nanoparticle surface. Covalent attachment or grafting is more effective than simple adsorption of PEG to the particle surface for preventing opsonization [26]. Generally, neutral and hydrophilic particles undergo much lower opsonization than do charged and hydrophobic particles [34]. While PEG is hydrophilic and has a neutral charge, it prevents hydrophobic and electrostatic interactions with the plasma proteins, thus avoiding opsonization. At the same time it also indicates the minimal or negligible role of PEG 400 because of its lack of capability to provide stealth to high molecular weight of PM181104. For the effective stabilization of CDDS, most of the studies showed that the protein adsorption decreased with an increase of polymer molecular weight (MW). Usually, the PEG with an MW of 2 kDa or higher provides better steric hindrance in avoiding opsonization [26] and most of authors supported an efficient MW in the range of 1500–3500 Da [29].