Enhancement of oral bioavailability of cyclosporine A: comparison of various nanoscale drug-delivery systems.
A variety of nanoscale delivery systems have been shown to enhance the oral absorption of poorly water-soluble and poorly permeable drugs. However, the performance of these systems has seldom been evaluated simultaneously. The aim of this study was to compare the bioavailability enhancement effect of lipid-based nanocarriers with poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to highlight the importance of the lipid composition, with cyclosporine A (CyA) as a model drug. CyA-loaded PLGA NPs, nanostructured lipid carriers (NLCs), and self-microemulsifying drug-delivery systems (SMEDDS) were prepared. The particle size of PLGA NPs (182.2 ± 12.8 nm) was larger than that of NLCs (89.7 ± 9.0 nm) and SMEDDS (26.9 ± 1.9 nm). All vehicles are charged negatively. The entrapment efficiency of PLGA NPs and NLCs was 87.6%± 1.6% and 80.3%± 0.6%, respectively. In vitro release tests indicated that the cumulative release of CyA was lower than 4% from all vehicles, including Sandimmun Neoral(®), according to the dialysis method. Both NLCs and SMEDDS showed high relative oral bioavailability, 111.8% and 73.6%, respectively, after oral gavage administration to beagle dogs, which was not statistically different from commercial Sandimmun Neoral(®). However, PLGA NPs failed to achieve efficient absorption, with relative bioavailability of about 22.7%. It is concluded that lipid-based nanoscale drug-delivery systems are superior to polymeric NPs in enhancing oral bioavailability of poorly water-soluble and poorly permeable drugs.
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai, People's Republic of China ; West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China ; Tropical Crops Genetic Resources Institute, Hainan Provincial Engineering Research Center for Blumea Balsamifera, Chinese Academy of Tropical Agricultural Sciences, Danzhou, Hainan, People's Republic of China.
Kai
K
Wang
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai, People's Republic of China.
Jianping
J
Qi
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai, People's Republic of China ; West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Tengfei
T
Weng
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai, People's Republic of China.
Zhiqiang
Z
Tian
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai, People's Republic of China.
Yi
Y
Lu
Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Kaili
K
Hu
West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Zongning
Z
Yin
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai, People's Republic of China.
Wei
W
Wu
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*
D004337:Drug Carriers; D004655:Emulsions; D016572:Cyclosporine
PLGA nanoparticle; bioavailability; cyclosporine A; nanostructured lipid carrier; self-microemulsifying drug-delivery systems