Atorvastatin (AT) is a widely used lipid-regulating drug to reduce cholesterol and triglycerides. Its poor aqueous solubility and hepatic metabolism require development of drug delivery systems able to improve its solubility and bypass hepatic effect. For this purpose, atorvastatin nanostructured lipid carriers (AT-NLCs) were prepared and characterized. AT-NLCs were prepared by emulsification using high-speed homogenization followed by ultrasonication. The prepared NLCs showed particle size between 162.5 ± 12 and 865.55 ± 28 nm while zeta potential values varied between À34 ± 0.29 and À23 ± 0.36 mV. They also showed high encapsulation efficiency (>87%) and amorphous state of the drug in lipid matrix. Pharmacokinetic parameters of optimized formulation (NLC-1; composed of 2% Gelucire V R 43/01, 8% Capryol V R PGMC, 2% Pluronic V R F68 and 0.5% lecithin) revealed 3.6-and 2.1-fold increase in bioavailability as compared to atorvastatin suspension and commercial product (Lipitor V R ), respectively. Administration of NLC-1 led to significant reduction (p < .05) in the rats' serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and significant increase in highdensity lipoprotein (HDL). This improvement was confirmed histologically by minimizing the associated hepatic steatosis. These investigations demonstrated the superiority of NLCs for improvement of oral bioavailability and in vivo performance of AT.
ARTICLE HISTORY
This study investigates the respirability and efficacy of peptide-micelle hybrid nanoparticles as carriers for inhalational therapy of pulmonary arterial hypertension (PAH). CARSKNKDC (CAR), a cell penetrating and lung homing peptide, conjugated DSPE-PEG micelles containing fasudil, an investigational anti-PAH drug, were prepared by solvent evaporation method and characterized for various physicochemical properties. The pharmacokinetics and pharmacological efficacy of hybrid particles containing fasudil were evaluated in healthy rats and monocrotaline induced PAH rats, respectively. CAR-micelles containing fasudil had an entrapment efficiency of ∼58%, showed controlled release of the drug, and were monodispersed with an average size of ∼14nm. NMR scan confirmed the drug's presence in the core of peptide-micelle hybrid particles. Compared with plain micelles, CAR peptide increased the cellular uptake by ∼1.7-fold and extended the drug half-life by ∼5-fold. The formulations were more prone to accumulate in the pulmonary vasculature than in the peripheral blood, which is evident from the ratio of the extent of reduction of pulmonary and systemic arterial pressures. On the whole, this study demonstrates that peptide-polymer hybrid micelles can serve as inhalational carriers for PAH therapy.
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