Pharmaceutical NanotechnologyA High-Drug-Loading Self-Assembled Nanoemulsion Enhances the Oral Absorption of Probucol in Rats
Section snippets
INTRODUCTION
With few exceptions, the effectiveness of orally administrated drugs significantly depends on their systemic exposure following oral delivery.1 However, approximately 30% of commercial drugs and 40% of new drug candidates are poorly soluble in water and exhibit too low oral bioavailability, which present the major hurdles to their clinical application.2., 3. Alternatively, many poorly water-soluble drugs have to be administered with higher dose to achieve the therapeutic efficacy.4., 5.
Materials
Probucol (purity 99.7%) was purchased from Wuyi Ci- hang Pharmaceutical Company Ltd. (Hebei, China). Solutol®HS-15 was obtained from BASF (Ludwigshafen, Germany) and medium-chain triglycerides (MCTs) were kindly gifted by Gattefosse (Saint Priest Cedex, France). Tween 80 was provided by the Sinopharm Chemical Reagent Company Ltd. (Shanghai, China). All other chemicals and solvents were of analytical or high-performance liquid chromatography (HPLC) grade.
Preparation of PSN
Probucol, Solutol®HS-15 (BASF), MCT, and
Preparation and Characterization of PSN
Self-assembled nanoemulsion (SN) was designed to improve the oral absorption of poorly water-soluble drugs with high dosing. The hydrophobic drugs could be entrapped into the lipophilic core of nanoemulsion consisting of oil and hydrophobic part of surfactant and stabilized with the hydrophilic surface, which could be effective to improve the aqueous solubility and oral absorption of poorly water-soluble drugs.14 In the present study, probucol was loaded into the SN with a high drug loading of
CONCLUSIONS
A high-drug-loading SN was developed to improve the oral absorption of poorly water-soluble probucol with high dosing. The PSN was homogeneous nanometersized droplets with the mean diameter of 40.32 ± 0.31 nm. The aqueous solubility of probucol was remarkably increased after its incorporation into PSN. Compared with free probucol suspension, the intestinal absorption of PSN was not significantly enhanced in duodenum, but obviously increased 3.62- and 13.1- fold in jejunum and ileum, respectively.
ACKNOWLEDGMENTS
The National Basic Research Program of China (2009CB930304, 2013CB932503, and 2013CB932704), Shanghai Rising-Star Program (11QA1407900), and SA-SIBS Scholarship Program are gratefully acknowledged for financial support.
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Zhiwen Zhang and Jian Huang contributed equally to this work.