The development of novel microneedle arrays fabricated from hyaluronic acid, and their application in the transdermal delivery of diabetes drugs

.........................................................................................................................2 INTRODUCTION ................................................................................................................6 CHAPTER 1 CHARACTERISTICS OF NOVEL MICRONEEDLE ARRAYS FABRICATED FROM HYALURONIC ACID ................................................................. 10 1.1. Materials ...................................................................................................................... 11 1.2. Fabrication of hyaluronic acid microneedle arrays .................................................... 11 1.3. Penetration capacity of hyaluronic acid microneedle arrays ..................................... 13 1.4. Visualization of micropores created by insertion of microneedle arrays ................... 14 1.5. Diffusion of FD4 in human skin with microneedle arrays containing FD4 ............... 15 1.6. Dissolution of microneedle arrays in rat skin ............................................................. 16 1.7. Determination of transepidermis water loss ............................................................... 17 1.8. Determination of transcutaneous electrical resistance ............................................... 19 1.9. Skin primary irritation test ......................................................................................... 21 1.10. In vivo dermatoscope observation ............................................................................. 23 1.11. In vitro transdermal delivery of FD4 by hyaluronic acid microneedle arrays ......... 24 CHAPTER 2 APPLICATION IN THE TRANSDERMAL DELIVERY OF DIABETES DRUGS ............................................................................................................................... 29 2.1. Materials ...................................................................................................................... 29 2.2 Application in the transdermal delivery of insulin with insulin-loaded microneedle arrays .................................................................................................................................. 30 2.2.1. Fabrication of insulin-loaded microneedle arrays ................................................ 30 2.2.2. Determination of insulin contents in insulin-loaded microneedle arrays ............ 32 2.2.3. Hygroscopy of insulin-loaded microneedle arrays ............................................... 32 2.2.4. Stability of insulin-loaded microneedle arrays ..................................................... 34 2.2.5. In vitro release of insulin from microneedle arrays .............................................. 35 2.2.6. In vivo transdermal absorption of insulin in diabetic rats ................................... 36 2.3 Application in the transdermal delivery of exendin-4 using tip-loaded microneedle arrays .................................................................................................................................. 43 2.3.1. Determination of drug contents in tip-loaded microneedle arrays ...................... 44 2.3.2. In vitro release study .............................................................................................. 46 2.3.3. Acute efficacy in Intraperitoneal glucose tolerance tests ..................................... 47 DISCUSSION ..................................................................................................................... 52 CONCLUSION ................................................................................................................... 55 ACKNOWLEDGMENTS .................................................................................................. 56 REFERENCES ................................................................................................................... 57 PUBLISHED PAPERS ....................................................................................................... 65