Directed Self-assembled Nanoparticles of Probucol Improve Oral Delivery: Fabrication, Performance and Correlation
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We are reporting on the development of a unique drug delivery platform by directed self-assembly technique to improve the oral delivery of hydrophobic drugs.
Herein, a series of probucol directed self-assembled nanoparticles (PDN) were developed with two components of probucol and surfactant such as Tween 20, Tween 80, D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS) and HS-15, which was respectively named as T20-PDN, T80-PDN, TP-PDN and HS-PDN. The formation of various PDNs was determined by in vitro characterization and the physicochemical properties of these PDNs were determined. Moreover, the performance of PDN in enhancing the oral delivery and possible correlation between the in vitro properties and in vivo performances were investigated.
PDN was homogenous nanometer-sized particles with negative surface charge. The cellular uptake of probucol in Caco-2 cell monolayer was respectively increased 1.15, 1.82, 1.59 and 5.31-fold by these PDN. In particular, the oral bioavailability of these PDN was significantly improved 3.0, 4.1, 5.4 and 10.4 folds compared with the free drug suspension. The enhanced cellular uptake and oral bioavailability were correlated with the characters of involved surfactants and the particle size of PDN.
Thereby, the directed self-assembled nanoparticles could provide a new strategy for enhancing the oral delivery of hydrophobic drugs.
KEY WORDScorrelation directed self-assembly nanoparticles oral delivery probucol
ACKNOWLEDGMENTS AND DISCLOSURES
Zhiwen Zhang and Shijun Jiang contributed equally to this work.
The National Basic Research Program of China (2013CB932503 and 2013CB932704), the National Natural Science Foundation of China (81270047, 81373359) and SA-SIBS Scholarship Program are gratefully acknowledged for financial support.