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• W2893822198 abstract "Aliskiren (ALS) is a direct renin inhibitor with low bioavailability and high drug cost. The goal of this study was to increase the bioavailability of ALS through nanoformulation. The optimized formulation was then evaluated in spontaneously hypertensive rats (SHRs). We developed an ALS poly(lactic- co-glycolic) acid nanoparticle (ALS-NP) through the emulsion–diffusion–evaporation method with various solvents, stabilizer concentrations, and centrifugation speeds. SHRs were orally dosed with 30 mg/kg ALS or dose equivalent ALS-NP. Several parameters were assayed in plasma and/or urine at baseline and 24 h post-dose, while pharmacokinetic analysis included serial sampling. The optimum formulation was found with ethyl acetate, a 1.00% w/v didodecyldimethylammonium bromide concentration, and a 10,000 r/min (15,554 g) centrifugation speed. A 168% relative bioavailability was observed as a result of ALS-NP administration along with significant, as determined by Student’s t-test, increases in the maximum ALS plasma concentration ( p = 0.0189) and the area under the plasma concentration–time curve from 0 to infinity ( p = 0.0095). Conversely, a reduction was found in oral volume of distribution ( p = 0.0009) and oral clearance ( p = 0.0298). Blood urea nitrogen increased significantly after dosing in both groups ( p < 0.0001 and p < 0.0001); however, no statistical difference was found between endpoint levels ( p > 0.05) following one-way analysis of variance (ANOVA). Kidney injury molecule-1 increased following ALS dosing ( p = 0.0486), while ALS-NP showed a decrease ( p = 0.027) which was also significantly decreased compared to ALS-Final ( p = 0.0008) when examined using two-way ANOVA. Urinary potassium excretion decreased significantly, as shown by two-way ANOVA, only in the ALS group ( p = 0.0274) which was also significantly reduced compared to ALS-NP-Final ( p = 0.016). Using the current formulation and at the dosage tested, ALS-NP showed a more favorable pharmacokinetic profile and positive kidney changes compared to ALS in regard to select outcomes. Thus, NP formulation may further improve ALS renoprotection in addition to increasing bioavailabilty." @default.
• W2893822198 created "2018-10-05" @default.
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• W2893822198 date "2018-01-01" @default.
• W2893822198 modified "2023-09-26" @default.
• W2893822198 title "Formulation and in vivo evaluation of aliskiren-loaded poly(lactic-co-glycolic) acid nanoparticles" @default.
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• W2893822198 doi "https://doi.org/10.1177/2397847318801155" @default.
• W2893822198 hasPublicationYear "2018" @default.
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