Glyceryl Monooleate/Poloxamer 407 Cubic Nanoparticles as Oral Drug Delivery Systems: I. In Vitro Evaluation and Enhanced Oral Bioavailability of the Poorly Water-Soluble Drug Simvastatin |
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Authors: | Jie Lai Jianming Chen Yi Lu Jing Sun Fuqiang Hu Zongning Yin Wei Wu |
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Institution: | (1) Department of Pharmaceutics, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China;(2) Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China;(3) School of Pharmacy, Second Military Medical University, Shanghai, 200433, China;(4) School of Pharmacy, Zhejiang University, Hangzhou, 310058, China; |
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Abstract: | Glyceryl monooleate (GMO)/poloxamer 407 cubic nanoparticles were investigated as potential oral drug delivery systems to enhance
the bioavailability of the water-insoluble model drug simvastatin. The simvastatin-loaded cubic nanoparticles were prepared
through fragmentation of the GMO/poloxamer 407 bulk cubic-phase gel using high-pressure homogenization. The internal structure
of the cubic nanoparticles was identified by cryo-transmission electron microscopy. The mean diameter of the cubic nanoparticles
varied within the range of 100–150 nm, and both GMO/poloxamer 407 ratio and theoretical drug loading had no significant effect
on particle size and distribution. Almost complete entrapment with efficiency over 98% was achieved due to the high affinity
of simvastatin to the hydrophobic regions of the cubic phase. Release of simvastatin from the cubic nanoparticles was limited
both in 0.1 M hydrochloride solution containing 0.2% sodium lauryl sulfate and fasted-state simulated intestinal fluid with
a total release of <3.0% at 10 h. Pharmacokinetic profiles in beagle dogs showed sustained plasma levels of simvastatin for
cubic nanoparticles over 12 h. The relative oral bioavailability of simvastatin cubic nanoparticles calculated on the basis
of area under the curve was 241% compared to simvastatin crystal powder. The enhancement of simvastatin bioavailability was
possibly attributable to facilitated absorption by lipids in the formulation rather than improved release. |
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