The Passive Targeting and the Cytotoxicity of Intravenous 10-HCPT Nanosuspension

Study on Formulation, in vivo Exposure, and Passive Targeting of Intravenous Itraconazole Nanosuspensions

“…The results of tissue distribution of ITZ further confirmed that RES-related organs, containing liver, lung, and spleen, could potentially serve as a drug reservoir depot for prolonged effect. Similar consequences were also discovered by others for clofazimine, 10-HCPT, and curcumin nanosuspensions (Peters et al., 2000; Pu et al., 2012; Bi et al., 2017). Another noticeable result from Figure 5 and Table 3 is that the ITZ concentration in the kidney is lower for ITZ-Nanos compared with ITZ injections, which is a potential advantage of ITZ-Nanos in reducing the toxicity of the drug to kidney.…”

“…In addition, the MRT (2.92 ± 0.39 h) and the half-life ( t 1/2 , 2.31 ± 0.25 h) of the ITZ-Nanos were longer than those observed of the ITZ injections (2.67 ± 0.22 h, 1.55 ± 0.08 h). This could be due to that ITZ-Nanos were partly recognized and captured by reticuloendothelial system (RES) and subsequently released back into the systemic circulation gradually (Peters et al., 2000; Pu et al., 2012). As reported in literatures, phagocytosis of nanoparticles by RES organs following I.V.…”

“…It can be seen from Table 3 that the concentrations of ITZ in liver, lung, and spleen were remarkably higher for ITZ-Nanos compared to those of ITZ injections, and the R e and C e values in the three tissues were larger than those in other tissues, suggesting ITZ-Nanos passively targeted to these organs. This could be due to that ITZ-Nanos were recognized as foreign substances and quickly endocytosed by phagocytes of the mononuclear phagocyte system (MPS) in blood circulation (Pu et al., 2012). The results of tissue distribution of ITZ further confirmed that RES-related organs, containing liver, lung, and spleen, could potentially serve as a drug reservoir depot for prolonged effect.…”

“…Nanosuspensions have been used to deliver the poorly soluble ITZ using various stabilizers, such as poloxamer 407 (Matteucci et al., 2006), Hydroxypropyl methyl cellulose (HPMC) (Matteucci et al., 2007; Matteucci et al., 2009), Polyvinyl alcohol and glycyrrhizinic acid (Fernández-Ronco et al., 2015), poloxamer 188 and sodium deoxycholate (Rabinow et al., 2007), tween 80 (Wlaz et al., 2015), the hybrid of HPMC and sodium dodecylbenzene sulfonate (SDS) (Azad et al., 2016), and tween 20 (Foglio Bonda et al., 2016). As many of these formulations have various limitations such as large particle size, poor stability, or toxicity for intravenous administration (Decuzzi et al., 2010; Pu et al., 2012), a new stabilizer, polyethylene glycol-poly(Benzyl aspartic acid ester) (PEG-PBLA), has been employed to stabilize ITZ nanoparticles (Zong et al., 2017). The PEG-PBLA-stabilized ITZ nanosuspensions (ITZ-Nanos) were fabricated by a combination of microprecipitation and high-pressure homogenization (mPHPH) method (Zong et al., 2017).…”

Formulation and characterization of biocompatible and stable I.V. itraconazole nanosuspensions stabilized by a new stabilizer polyethylene glycol-poly(β-Benzyl- l -aspartate) (PEG-PBLA)

“…Various stabilizers have been used in ITZ Nano disperse systems, including poloxamer 407 (Matteucci et al, 2006), HPMC (Matteucci et al, 2007;Matteucci et al, 2009), poloxamer 188 and sodium deoxycholate (Rabinow et al, 2007), poly (vinyl alcohol) and glycyrrhizic acid (Fernández-Ronco et al, 2015), Tween 80 (Wlaz et al, 2015), HPMC and SDS (Azad et al, 2016) and Tween 20 (Foglio Bonda et al, 2016) . However, formulations using these stabilizers have their limitations, such as large size up to a micron or unknown stability, and are not suitable for intravenous administration as they could bring potential safety issues (Decuzzi et al, 2010;Pu et al, 2012). To overcome such limitations, it is desirable to have new stabilizers that are able to adsorb onto the surface of the particles more firmly and hence providing better stabilizing effect.…”