Evaluation of AML-VAL Nanoparticles as Combined Therapy in Cardiovascular Disease

Abstract

The main aim of this study was to investigate a mixture of two poorly water-soluble active pharmaceutical ingredients (APIs): an angiotensin II receptor antagonist (valsartan) and a calcium channel blocker (amlodipine besylate), chosen in a fixed-dose, in order to obtain new polymeric nanoparticles (NPs) for cardiovascular diseases treatment. NPs were prepared via nanoprecipitation method using poly (D,L-lactide-co-glycolide) (PLGA) as matrix and Pluronic F127 as stabilizer. Three formulations were investigated with different ratios of AML:VAL:PLGA (1:16:5, 1:16:7.5 and 1:16:10). Particle size, polydispersity index and zeta-potential analyses were performed to characterize and optimize the formulation. The in vitro drug release study was determined by using a dialysis membrane method under sink conditions. All NPs loaded with both APIs showed nano-size, negative potential, a high homogeneity and a slow drugs release in physiological environment.

Intracellular Uptake Study of Polymeric Nanoparticles Loaded with Cardiovascular Drugs Using Confocal Laser Scanning Microscopy

“…A mixture of two cardiovascular drugs-valsartan (an angiotensin II receptor antagonist drug) and amlodipine besylate (a calcium channel blocker)-was loaded in polymeric nanoparticles. The formulation of PLGA NPs loaded with valsartan-amlodipine (PLGA:valsartan:amlodipine besylate = 10:16:1) was established in prevoius studies [8,9] as optimal having high EE (%) for both drugs (91.98 ± 0.18% for valsartan and 82.54 ± 0.12% for amlodipine besylate, nano-metric particle size (140.4 ± 1.34 nm) and narrow dispersity (polydispersity index = 0.108 ± 0.03). The cellular uptake of polymeric nanoparticles was investigated by incubating adherent mouse embryo fibroblasts (NIH 3T3) with a suspension of PLGA NPs loaded with valsartanamlodipine.…”

“…PLGA NPs loaded with valsartan-amlodipine were synthesized via nanoprecipitation method according to previous reports [8,9]. Briefly, PLGA and cardiovascular drugs were dissolved in acetone (organic phase), while Pluronic-F127 was dissolved in distilled water (aqueous phase).…”

Evaluation of drug release kinetics from polymeric nanoparticles loaded with poorly water-soluble APIs

“…PLGA nanoparticles loaded with AML-VAL were prepared by nanoprecipitation method as described elsewhere [19,20] using PLGA, as biodegradable polymeric and an amphiphilic block copolymer -Pluronic F127 as stabilizer. The composition of prepared PLGA nanoparticles loaded with AML-VAL is presented in Table 1.…”

“…In previous studies we evaluated several nanoformulations with different quantities of PLGA and we concluded that in the range of concentrations 5-60 mg PLGA and at a stirring rate of 1200-1500 rpm cardiovascular drugs loaded nanoparticles with good features can be obtained [19,20]. However, the release behavior has only been studied for the nanoformulations with 5, 7.5 and 10 mg PLGA [20].…”

“…In previous studies we evaluated several nanoformulations with different quantities of PLGA and we concluded that in the range of concentrations 5-60 mg PLGA and at a stirring rate of 1200-1500 rpm cardiovascular drugs loaded nanoparticles with good features can be obtained [19,20]. However, the release behavior has only been studied for the nanoformulations with 5, 7.5 and 10 mg PLGA [20]. The aim of this research was to investigate the release behavior of a combination of two poorly water-soluble APIs from PLGA nanoparticles with higher PLGA concentrations, in the range of 25-50 mg. Amlodipine besylate (AML), a calcium channel blocker, and valsartan (VAL), an angiotensin II receptor antagonist drug, were used as poorly water-soluble model drugs.…”