title: Supersaturated polymeric micelles for oral cyclosporine A delivery: The role of Soluplus-sodium dodecyl sulfate complex.
abstract: Our previous study demonstrated that the retention of drug in the hydrophobic core of Soluplus micelle greatly impeded drug absorption from gastrointestinal tract. Using supersaturated polymeric micelles can improve drug release, however, insufficient maintaining of supersaturation of drug is still unfavorable for drug absorption. Here, we report adding small amount of small molecule, sodium dodecyl sulfate (SDS), to Soluplus solution can form a Soluplus-SDS complex. This complex not only showed a higher solubilization capability for the model drug cyclosporine A (CsA), but also maintained a longer period of and higher supersaturation than was achieved with Soluplus alone. The Soluplus-SDS interactions were characterized by analyzing surface tension, small-angle X-ray scattering (SAXS), fluorescence spectra, and nuclear magnetic resonance spectroscopy. The results demonstrated that the formation of Soluplus-SDS complex via SDS adsorption on hydrophobic segments of Soluplus, which have more hydrophobic domain than that of Soluplus micelle, contributed significantly to the solubilization and stabilization of supersaturated CsA. Using this amphiphilic copolymer-small molecule surfactant system, the cellular uptake and rat in vivo absorption of CsA were more effectively achieved than pure Soluplus. The area under the plasma concentration-time curve (AUC) and the maximal plasma concentration (Cmax) achieved by CsA-loaded Soluplus-SDS complex were 1.58- and 1.8-times higher than the corresponding values for CsA-loaded pure Soluplus, respectively. This study highlighted the benefits of Soluplus-SDS complex for optimizing the solubilization and oral absorption of a drug with low aqueous solubility.
authors: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 501, Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China.
authors: Dengning
authors: D
authors: Xia
authors: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 501, Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China.
authors: Hongzhen
authors: H
authors: Yu
authors: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 501, Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China; Department of Pharmacy, Medical College of Nanchang University, Nanchang 330066, China.
authors: Jinsong
authors: J
authors: Tao
authors: Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
authors: Jianrong
authors: J
authors: Zeng
authors: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 501, Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China.
authors: Quanlei
authors: Q
authors: Zhu
authors: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 501, Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China.
authors: Chunliu
authors: C
authors: Zhu
authors: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 501, Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China. Electronic address: simm2122@vip.sina.com.
authors: Yong
authors: Y
authors: Gan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D018938:Caco-2 Cells; D016572:Cyclosporine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008823:Micelles; D018613:Microscopy, Confocal; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D053838:Scattering, Small Angle; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*; D012995:Solubility; D013500:Surface Tension; D014961:X-Ray Diffraction
chemical_list: D007166:Immunosuppressive Agents; D008823:Micelles; D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D012967:Sodium Dodecyl Sulfate; D011092:Polyethylene Glycols; D016572:Cyclosporine
keywords: Amphiphilic polymer–ionic surfactant interaction; Sodium dodecyl sulfate; Solubilization; Soluplus; Supersaturation