And this observation is in good agreement with other parameters
measured for the same series. The pH value of PM181104 formulations F1 to F8 was in the pH range of 3.40–6.32 (Table 3). It was observed that the pH value was decreased in proportion to the decreased concentrations of T-80. However, these observations were in reverse with the decreasing concentrations of PEG 400. Knowing that the extreme pH selleck chemical (both alkaline and acidic) could be susceptible for peripheral vein rupture, the pH of the infusion solution is generally expected to be between 5 and 9 [25]. Interestingly, here in our studies, all the efficacious formulations fulfilled the pH criteria required for intravenous administration. The plot of plasma concentration vs. time for PM181104 after intravenous administration of formulations F1 to F8 in mice are shown in Fig. 4. Formulations F1 and F2 showed higher plasma exposure of the drug (AUClast averaged above 9.0 µg h mL−1
and C0 averaged above 80 µg h mL−1) are shown in Fig. 5a and b and the corresponding pharmacokinetic parameter values in Table 1. An important component of in vivo performance of nanoparticulate systems is the opsonization Dabrafenib solubility dmso and clearance of particles by the mononuclear phagocytic system or the reticuloendothelial system (RES). Opsonization is the process by which a particle becomes covered with the so-called opsonin proteins [26]. The improved behavior of these formulations (F1 and F2) could be due to the stealth associated with smaller particle size of the drug (below 100 nm) that might help to escape the process of opsonization and phagocytosis by reticuloendothelial system (RES) during blood circulation, resulting in higher plasma concentration of the drug ( Fig. 2). Moreover, the size
of the particle and its surface modification are able to strongly influence the proteins adsorbed on the nanoparticle surface. Lower protein adsorption is seen with smaller nanoparticles (70 nm) than with the larger nanoparticles (≥200 nm) [27] and [28]. Studies have shown that smaller particle size of the drug have an advantage as is evident from the fact that colloidal drug delivery systems (CDDS) have a tendency to be removed slowly from the blood circulation then the larger particles [10] and [29]. In vivo efficacy of PM181104 SDHB with the formulation F1 in tissue or organ specific infection models (against MRSA and VRE) showed a reduction in the bacterial titer when compared to standard antibiotics (Linezolid and Vancomycin) [5]. However unlike the F1 and F2, the situation in case of formulations F3–F5 was different. These formulations showed lower plasma exposure compared to F1 and F2 (AUClast averaged below 5.0 µg h mL−1 and C0 averaged below 70 µg h mL−1) are shown in Fig. 5a and b and the corresponding pharmacokinetic parameter values in Table 1.