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  • Title: Spray-Dried Silica Xerogel Nanoparticles as a Promising Gastroretentive Carrier System for the Management of Chemotherapy-Induced Nausea and Vomiting.
    Author: Ghoneim AM, Tadros MI, Alaa-Eldin AA.
    Journal: Int J Nanomedicine; 2019; 14():9619-9630. PubMed ID: 31824155.
    Abstract:
    PURPOSE: The current work aimed to develop spray-dried silica xerogel nanoparticles (SXNs) as a gastroretentive carrier for the dual delivery of chlorambucil (CHL) and granisetron hydrochloride (GR). As a low-density system, it was proposed to float over gastric fluids; allowing for the retention of CHL in the acidic medium where it is more stable while ensuring the solubility of GR. METHODS: Silica xerogels were developed by sol-gel process, using Tetraethyl orthosilicate (TEOS) water and acetic acid, followed by spray drying. SXNs were evaluated for particle size, zeta potential, entrapment efficiency (EE%), CHL and GR release after 1 hr (P1h) and after 8 hrs (P8h). The best achieved system (SXN4) was evaluated for morphology, pore diameter, total porosity, bulk density, wetting time, floating characteristics. Furthermore, the pharmacokinetics of the loaded drugs were evaluated in rats; relative to an aqueous CHL suspension containing GR. RESULTS: SXN4 system had the highest desirability (0.69); showing spherical nanoparticles (181.63 nm), negative zeta potential (-5.18 mV), promising EE% of 59.39% and 73.94% (for CHL and GR, respectively) and sustained CHL and GR release profiles characterized by low P1h (22.75% and 30.74%) and high P8h (60.36% and 99.33%), respectively. It had a mean pore diameter of 8.622 nm, a total porosity of 62.27%, a bulk density of 0.605 g/mL, a wetting time of 292 sec, zero lag time and a floating duration of at least 8 h. CONCLUSION: The prolongation in the mean residence time (MRT(0-∞)) and the promotion of the relative oral bioavailabilities of both drugs could unravel the potential of this system for the management of chemotherapy-induced nausea and vomiting.
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