| Summary: | 碩士 === 國立成功大學 === 化學工程學系碩博士班 === 100 === ABSTRACT
Recently, various polymeric microneedle devices have been developed for painless and self-administration transdermal delivery of biopharmaceuticals. However, most of polymer microneedles are rapidly dissolved and only for burst release. Additionally, these polymer materials are mechanically weaker than metal or silicon and thus result in incomplete insertion of microneedles and some waste of drugs. In this study, we developed a biodegradable transdermal microneedle device, which combined chitosan microneedles with a poly (L-lactide-co-DL-lactide) (PLA) supporting base, and it can be fully embedded inside the skin after insertion. To prevent damaging the integrity of encapsulated biomolecules, a gentle fabrication process for chitosan microneedle was developed. In vitro porcine skin insertion test showed that the insertion ratio and penetration depth of chitosan microneedle patch were 100% and 550 ± 50 μm, respectively. This penetration depth corresponded to insertion across the epidermis layer into the dermis layer where antigen-presenting cells are abundantly present. After insertion, the chitosan microneedle can be separated from the PLA supporting base and be left in the skin for sustained drug release. In vitro drug delivery study indicated that encapsulated model drugs can be released from chitosan microneedles for at least one week, indicating that the embeddable microneedle patch has potential for long-term drug treatment. In vivo degradability study showed that the embedded chitosan microneedle was gradually degraded within the rat skin over time for at least 2 weeks. In the rat immunization study, the model antigen—ovalbumin (OVA) released from the chitosan microneedles induced similar IgG antibody production with intramuscular injection at the same dosage (1 mg). This result indicated that the integrity of OVA still remained after the microneedle fabrication process. In conclusions, we believe that this embeddable and degradable microneedle patch can be an attractive alternative for transdermal delivery of vaccines or other macromolecular drugs.
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