Drug Design, Development and Therapy (Jun 2019)
Solutol®HS15+pluronicF127 and Solutol®HS15+pluronicL61 mixed micelle systems for oral delivery of genistein
Abstract
Pinggang Ding,1,2,* Yuxuan Chen,3,* Guangshang Cao,4 Hongxue Shen,1,2 Jianming Ju,1,2 Weiguang Li,51Department of Pharmaceutical Analysis and Metabolomics, Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, People’s Republic of China; 3School of Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 4Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 5Department of Marine Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China*These authors contributed equally to this work Purpose: We aimed to prepare two oral drug delivery systems consisting of polyoxyl 15 hydroxystearate (HS15) with pluronicF127 (F127) and HS15 with pluronicL61 (L61) to overcome the challenges of genistein’s poor oral bioavailability. This provides a good strategy for enhancing the potential value of genistein.Methods: We designed two binary mixed micelle systems employing the organic solvent evaporation method using surfactants (HS15, L61, and F127). Formulations (GEN-F and GEN-L) were characterized by transmission electron microscopy. Drug content analysis, including entrapment efficiency (EE%), drug loading (DL%), and the cumulative amount of genistein released from the micelles, was performed using HPLC. The permeability of optimum formulation was measured in Caco-2 cell monolayers, and the oral bioavailability was evaluated in SD rats.Results: The solutions of GEN-F and GEN-L were observed to be transparent and colorless. GEN-F had a lower EE% of 80.79±0.55% and a DL% of 1.69±0.24% compared to GEN-L, which had an EE% 83.40±1.36% and a DL% 2.26±0.18%. TEM results showed that the morphology of GEN-F and GEN-L was homogeneous and resembled a spherical shape. The dilution and storage conditions had no significant effect on particle size and EE%. Genistein demonstrated a sustained release behavior when encapsulated in micelles. Pharmacokinetics study showed that the relative oral bioavailability of GEN-F and GEN-L increased by 2.23 and 3.46 fold while also enhancing the permeability of genistein across a Caco-2 cell monolayer compared to that of raw genistein.Conclusion: GEN-F and GEN-L as a drug delivery system provide an effective strategy for enhancing and further realizing the potential value of GEN.Keywords: genistein, micelles, polyoxyl 15 hydroxystearate, pluronicF127, pluronicL61, oral bioavailability
