title: Self-assembling bubble carriers for oral protein delivery.
abstract: Successful oral delivery of therapeutic proteins such as insulin can greatly improve the quality of life of patients. This study develops a bubble carrier system by loading diethylene triamine pentaacetic acid (DTPA) dianhydride, a foaming agent (sodium bicarbonate; SBC), a surfactant (sodium dodecyl sulfate; SDS), and a protein drug (insulin) in an enteric-coated gelatin capsule. Following oral administration to diabetic rats, the intestinal fluid that has passed through the gelatin capsule saturates the mixture; concomitantly, DTPA dianhydride produces an acidic environment, while SBC decomposes to form CO2 bubbles at acidic pH. The gas bubbles grow among the surfactant molecules (SDS) owing to the expansion of the generated CO2. The walls of the CO2 bubbles consist of a self-assembled film of water that is in nanoscale and may serve as a colloidal carrier to transport insulin and DTPA. The grown gas bubbles continue to expand until they bump into the wall and burst, releasing their transported insulin, DTPA, and SDS into the mucosal layer. The released DTPA and SDS function as protease inhibitors to protect the insulin molecules as well as absorption enhancers to augment their epithelial permeability and eventual absorption into systemic circulation, exerting their hypoglycemic effects.
authors.affiliation: Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Chuang
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: Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Po-Yen
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Department of Chemical Engineering and 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.
authors.forename: Shiaw-Pyng
authors.initials: SP
authors.lastname: Wey
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
authors.forename: Fwu-Long
authors.initials: FL
authors.lastname: Mi
authors.affiliation: Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Hsu-Chan
authors.initials: HC
authors.lastname: Hsiao
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan, Miaoli, Taiwan, ROC. Electronic address: ctchen@nhri.org.tw.
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
authors.affiliation: Department of Chemical Engineering and 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; D002214:Capsules / Q000633:toxicity; D045744:Cell Line, Tumor; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D004337:Drug Carriers / Q000633:toxicity; D005780:Gelatin; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007408:Intestinal Absorption; D045423:Microbubbles; D004369:Pentetic Acid; D010539:Permeability; D011506:Proteins / Q000008:administration & dosage*; D059748:Proteolysis / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012967:Sodium Dodecyl Sulfate / Q000008:administration & dosage / Q000633:toxicity; D012995:Solubility; D013608:Tablets, Enteric-Coated; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002214:Capsules; D004337:Drug Carriers; D007328:Insulin; D011506:Proteins; D013608:Tablets, Enteric-Coated; D012967:Sodium Dodecyl Sulfate; D004369:Pentetic Acid; D005780:Gelatin
keywords: Biodistribution; Colloidal carrier; Foaming agent; Oral protein delivery; Surfactant