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dc.contributorDepartment of Health Technology and Informaticsen_US
dc.creatorLeung, Cristina-
dc.publisherHong Kong Polytechnic University-
dc.rightsAll rights reserveden_US
dc.titleOral insulin delivery using pH-responsive hydrogel and gold nanoparticle hybrid carrieren_US
dcterms.abstractA huge number of diabetic patients require multi-daily subcutaneous insulin injections in order to maintain normal blood glucose level. This treatment option is painful and leads to low patient compliance. In view of this, oral administration has been actively investigated over the past two decades. For an effective delivery, the oral formulation needs to protect insulin against degradation along the gastrointestinal tract and to improve insulin uptake through the intestinal wall to the bloodstream. Poly(methacrylic acid) grafted with poly(ethylene glycol) (P(MAA-g-EG)), a pH-responsive hydrogel, is by far one of the most efficacious oral insulin delivery systems. Insulin is loaded into P(MAA-g-EG) microparticle at neutral pH, followed by an acidic collapse of the microparticle with interpolymer complexation to entrap the loaded insulin. At low pH in the stomach, the collapsed microparticle protects the entrapped insulin from enzymatic degradation. On the other hand, at neutral pH in the intestine, the microparticle swells and releases its insulin content. It should, however, be noted that only about 10% of the administered insulin can get into the bloodstream. Previous studies reported that about 40% of the loaded insulin leaked out at low pH environment because the pores in the collapsed microparticles are still too large so that the entrapped insulin could diffuse out.en_US
dcterms.abstractHerein, the utilization of gold nanoparticles as nanoplugs to reversibly block the surface pores of the collapsed microparticles was investigated. The gold nanoparticles were surface functionalized with insulin (AuNP-insulin) and the size of this conjugate was designed to match with that of the collapsed pore. Experimental results showed that the amount of insulin leakage with acidic treatment was reduced from 26% to 14% in insulin-loaded P(MAA-g-EG) microparticles without and with AuNP-insulin nanoplugs, respectively. Moreover, it was observed that 62% of the loaded insulin was expelled from the microparticles during the acidic collapse step. In other words, the loading efficiency was only 38%. When AuNP-insulin conjugate was used to plug the surface pores of the P(MAA-g-EG) microparticles prior to the collapse process, the loading efficiency was increased to 70%. Antigenic study with enzyme-linked immunosorbent assay (ELISA) on pepsin-containing simulated gastric fluid treatment of the insulin-loaded P(MAA-g-EG) microparticles confirmed that the enzyme could not get into the pores and degrade the entrapped insulin. Therefore, with the higher loading efficiency and less leakage, the plugged microparticles would be a more efficient carrier in delivering insulin to the small intestine, where absorption to bloodstream takes place. Surprisingly, the release of insulin and the AuNP-insulin conjugate from the plugged microparticle at neutral pH was found to have strong dependence on phosphate ion concentration. The release efficiency in phosphate-buffered saline (i.e., 1× PBS) containing 5.7 mM phosphate ions was 19% while that in sodium phosphate buffer containing 0.1 M phosphate ions was 43%. Besides insulin, the AuNP-insulin conjugate was released to the sodium phosphate buffer, but was kept within the microparticles in 1× PBS. The P(MAA-g-EG)-AuNP hybrid carrier developed in this study would contribute to the further improvement of the efficacy of oral protein drug delivery.en_US
dcterms.extentxxi, 103 p. : ill. ; 30 cm.en_US
dcterms.isPartOfPolyU Electronic Thesesen_US
dcterms.educationalLevelAll Masteren_US
dcterms.LCSHDiabetes -- Treatment.en_US
dcterms.LCSHDrug carriers (Pharmacy)en_US
dcterms.LCSHHong Kong Polytechnic University -- Dissertationsen_US
dcterms.accessRightsopen accessen_US

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