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    The studies of PLGA nanoparticles loading atorvastatin calcium for oral administration in vitro and in vivo

    Zhenbao Li;Wenhui Tao;Dong Zhang;Chunnuan Wu;Binbin Song;Shang Wang;Tianyang Wang;Mingming Hu;Xiaohong Liu;Yongjun Wang;Yinghua Sun;Jin Sun;School of Pharmacy, Shenyang Pharmaceutical University;Tianjin Medical University Cancer Hospital;China Resources Double-crane Pharmaceutical Co., Ltd.;Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University;  
    A biodegradable poly(lactic-co-glycolic acid) loading atorvastatin calcium(AC) nanoparticles(AC-PLGA-NPs) were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of AC. The effects of experimental parameters, including stabilizer species, stabilizer concentration and pH of aqueous phase, on particle size were also evaluated. The resultant nanoparticles were in spherical shape with an average diameter of 174.7 nm and a narrow particle size distribution. And the drug loading and encapsulation efficiency were about 8% and 71%, respectively. The particle size and polydispersion were almost unchanged in 10 days. The release curves of AC-PLGA-NPs in vitro displaying sustained release characteristics indicated that its release mechanisms were matrix erosion and diffusion. The pharmacokinetic study in vivo revealed that the C_(max) and AUC_(0-∞) of AC-PLGA-NPs in rats were nearly 3.7-fold and 4.7-fold higher than that of pure atorvastatin calcium suspension. Our results demonstrated that the delivery of AC-PLGANPs could be a promising approach for the oral delivery of AC for enhanced bioavailability.
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