title: Safety and efficacy of self-assembling bubble carriers stabilized with sodium dodecyl sulfate for oral delivery of therapeutic proteins.
abstract: Sodium dodecyl sulfate (SDS) is generally regarded as a potent permeability enhancer in oral formulations; however, one concern related to the use of any permeation enhancer is its possible absorption of unwanted toxins during the period of epithelial permeability enhancement. In this work, the safety and efficacy of an SDS-containing bubble carrier system that is developed from an orally administered enteric-coated capsule are evaluated. The bubble carriers comprise diethylene triamine pentaacetic acid (DTPA) dianhydride, sodium bicarbonate (SBC), SDS, and insulin. Upon exposure to the intestinal fluid, DTPA dianhydride hydrolyzes to yield acids, and SBC rapidly reacts with these acids to generate CO2, producing bubble carriers, each containing a self-assembling water film. The hydrophilic insulin is entrapped in the self-assembled water film, which is stabilized by SDS. The SDS in the bubble carrier system can act as a dissolution enhancer in the dispersion of insulin molecules, as a surfactant that stabilizes the bubble carriers, as a protease inhibitor that protects the protein drug, and as a permeation enhancer that augments its oral bioavailability. Hence, a significant increase in the plasma insulin level and an excellent blood glucose-lowering response in diabetic rats are effectively achieved. Moreover, the enhancement of epithelial permeation by this SDS-containing formulation does not promote the absorption of intestinal endotoxins. The above facts indicate that the bubble carrier system that is stabilized by SDS can be used as a safe and potent carrier in the oral delivery of therapeutic proteins.
authors.affiliation: Department of Chemical Engineering/Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Po-Yen
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan, ROC.
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Chuang
authors.affiliation: Department of Chemical Engineering/Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Chiu
authors.affiliation: Department of Chemical Engineering/Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Hsin-Lung
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.affiliation: Division of Endocrinology and Metabolism, Chang Gung University and Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Jyuhn-Huarng
authors.initials: JH
authors.lastname: Juang
authors.affiliation: Department of Chemical Engineering/Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Chiang
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC. Electronic address: flmi530326@tmu.edu.tw.
authors.forename: Fwu-Long
authors.initials: FL
authors.lastname: Mi
authors.affiliation: Department of Chemical Engineering/Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC. Electronic address: hwsung@mx.nthu.edu.tw.
authors.forename: Hsing-Wen
authors.initials: HW
authors.lastname: Sung
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D018938:Caco-2 Cells; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D004369:Pentetic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017693:Sodium Bicarbonate / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D012967:Sodium Dodecyl Sulfate / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D014357:Trypsin / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D012967:Sodium Dodecyl Sulfate; D004369:Pentetic Acid; D017693:Sodium Bicarbonate; D014357:Trypsin
keywords: Blood glucose-lowering effect; Diabetes mellitus; Endotoxin; Oral protein delivery; Permeability enhancer