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Fabrication and Characterization of Insulin Microneedle

초록/요약

본 연구의 목적은 hyaluronic acid가 기반이 된 insulin microneedle을 개발하고 이의 특성 및 효능을 평가하는 것이다. Microneedle은 최소 침습적이고 통증이 없는 방식으로 피부 각질층을 통해 insulin을 전달 할 수 있다. 이 문헌에서는 insulin을 함유한 dissolving microneedle에서 단백질 전달을 위한 microneedle의 포괄적인 특성 및 연구를 진행하였다. 우리의 dissolving microneedle은 생분해성 소재 중 하나인 hyaluronic acid를 포함하는 생분해성 약물전달시스템이다. Microneedle의 형태는 주사전자현미경과 실체현미경을 사용하여 관찰한 결과 약 625 μm의 길이를 나타냈다. 또한, 체외방출 연구를 통해 insulin이 microneedle에서 90분 이후에는 완전히 방출된다는 것이 입증됐다. 이후, 생체 내 혈당강하 연구를 통해 insulin microneedle은 최대 혈당강하시점이 1-2시간 이내로 피하주사와 동일하게 나타난다는 것을 확인했다. 따라서, 본 연구의 결과는 microneedle이 당뇨병 치료를 위한 유망한 방법이며, 효과적이고 안전한 경피 insulin 전달 방법임을 시사한다.

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초록/요약

The purpose of this study is to develop a hyaluronic acid-based insulin microneedle and to evaluate its morphological characteristic, axial force, release rate and amount. Microneedles can deliver insulin through the stratum corneum of the skin in a minimally invasive and painless manner. We conducted a comprehensive characterization and development of microneedles for protein delivery in an insulin containing dissolving microneedle. Our dissolving microneedles constitute a biodegradable drug delivery system incorporating hyaluronic acid, one of the biodegradable materials used in this study. The shape of the microneedle was examined using a scanning electron microscope and a stereo microscope, revealing a length of approximately 625 μm. In addition, in vitro release studies demonstrated complete insulin release from the microneedle within 90 minutes. Subsequently, through in vivo blood glucose lowering studies, it was confirmed that the insulin microneedle achieved the same maximum blood glucose reduction within 1–2 hours as a subcutaneous injection. Overall, the findings of this study suggest that this microneedle a promising method for the treatment of diabetes, serving as an effective and safe transdermal insulin delivery method.

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목차

Ⅰ. Introduction 1
Ⅱ. Material and Method 5
A. Materials 5
B. Methods 5
1. Fabrication of PDMS mold 5
2. Preparation of formulation 5
3. Preparation of insulin microneedles 7
4. Morphology of microneedles 7
5. Axial force test of microneedles 7
6. In vitro skin insertion test 8
7. Dissolving test of microneedles with and without insulin 10
8. Analysis of the insulin content and homogeneity 10
9. In vitro drug release profile of insulin microneedles 10
10. In vivo transdermal delivery of microneedles 12
Ⅲ. Results 13
A. Morphology of microneedles 13
B. Mechanical properties of microneedles 13
1. Axial force of microneedles 13
2. Insertion ratio of microneedles 17
C. Solubility of microneedles in agarose gel 20
D. Analysis of the insulin content and homogeneity 23
E. In vitro drug release profile of microneedles 23
F. In vivo drug release profile of microneedles 23
Ⅳ. Discussion 28
Ⅴ. Conclusions 30
Ⅵ. References 31
Korean Abstract 35

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