| Research Abstract |
Microneedles (MN) is a novel DDS for percutaneous delivery of peptide/proteins, vaccine and gene, DNA. Professor Takada innovated two types of MN, pen-type and patch type MN. MN is made of water-soluble polymer as the base, which contains drug as a supramolecular complex. After the administration of pen-type MN by inserting into the skin, base dissolves rapidly and releases drug that is absorbed into the systemic circulation. Proof-of-concept (POC) experiments were performed with insulin, EPO, IFN and growth hormone (GH), where high bioavailability, 70-99%, was obtained in mice, rats and dogs. For insulin, IFN and GH, the absorption rate is almost the same as subcutaneous injection preparation. EPO shows Tmax of 18 h, which suggests the absorption of EPO thorough lymphatic route. Safety study was performed with rats and dogs where evans blue (EB) was formulated into the MN in addition to insulin and EPO. After administration, ER was released from MN within 3 h. To prepare MN, supramolecular complex of drug is at first formed with thread-forming water-soluble polymer like dextran, chondroitin sulfate and albumin etc. Thereafter, MN is formed. The size of pen-type MN is about 2000μm length and 500μm in diameter. Also, patch type MN can be prepared. A machine to produce patch type MN was developed. With this machine, a patch having 16 MN on itself, 10cm^2 area, can be produced, where the length of MN is 500μm and the diameter of the bottom is 300 um. With the MN patch, insulin was formulated and pharmacodynamic study was performed. Hypoglycemic effect showed good dose-dependency in rats and was equivalent to insulin injection.
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