Effects of lipophilic emulsifiers on the oral administration of lovastatin from nanostructured lipid carriers: physicochemical characterization and pharmacokinetics.
Nanostructured lipid carriers (NLCs) made from mixtures of Precirol and squalene were prepared to investigate whether the bioavailability of lovastatin can be improved by oral delivery. The size, zeta potential, drug-loading capacity, and release properties of the NLCs were compared with those of lipid nanoparticles containing pure Precirol (solid lipid nanoparticles, SLNs) and squalene (lipid emulsions, LEs). Stable nanoparticles with a mean size range of 180-290 nm and zeta potential range of -3 to -35 mV were developed. More than 70% lovastatin was entrapped in the NLCs and LEs, which was significantly higher compared to the SLNs. The in vitro release kinetics demonstrated that lovastatin release could be reduced by up to 60% with lipid nanoparticles containing Myverol as the lipophilic emulsifier, which showed a decreasing order of NLCs>LEs>SLNs. Drug release was further decreased by soybean phosphatidylcholine (SPC) incorporation, with NLCs and SLNs showing the slowest delivery. The oral lovastatin bioavailability was enhanced from 4% to 24% and 13% when the drug was administered from NLCs containing Myverol and SPC, respectively. The in vivo real-time bioluminescence imaging indicated superior stability of the Myverol system over the SPC system in the gastric environment.
Chen
Chih-Chieh
CC
Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Taoyuan, Taiwan.
Tsai
Tung-Hu
TH
Huang
Zih-Rou
ZR
Fang
Jia-You
JY
D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D055598:Chemical Phenomena; D003692:Delayed-Action Preparations; D004075:Diglycerides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D045703:Emulsifying Agents / Q000737:chemistry*; D041981:Gastrointestinal Tract / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008148:Lovastatin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013185:Squalene / Q000737:chemistry; D013499:Surface Properties; D014018:Tissue Distribution
D000924:Anticholesteremic Agents; D003692:Delayed-Action Preparations; D004075:Diglycerides; D004337:Drug Carriers; D045703:Emulsifying Agents; D008055:Lipids; D010713:Phosphatidylcholines; D013185:Squalene; D008148:Lovastatin; C009032:precirol