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약물전달체와 유착방지제를 위한 전기방사된 나노섬유의 제조 및 적용

Application of electrospun nanofibers for drug carrier and anti-adhesion

초록/요약

Electrospinning is process that can produce nano-scale fibers continuously under the action of an externally imposed electric field from a polymeric solution or melt. By using an electrospinning process, it is possible to easily produce nanofibers all various polymeric materials that can be melted and mixed in a solvent. Also, nanofibers are easily adjustable in shape and size, and thus can be applied to various fields of biomedical applications. The aim of this thesis is to confirm the possibility of biomedical application of electrospun nanofiber sheet using natural and synthetic materials as drug carrier and anti-adhesion barrier. In the chapter 2, to develop a sustained dexamethasone (Dex) delivery system, poly(ε-caprolactone-co-L-lactide) copolymer with controllable biodegradability was synthesized and further utilized to prepare electrospun Dex-loaded nanofiber sheets using water-insoluble Dex or water-soluble Dex. The Dex-nanofiber sheets obtained by electrospinning exhibited randomly oriented and interconnected fibrillar structures. In addition, Dex-nanofiber sheets exhibited sustained in vitro and in vivo water-soluble Dex release for a prolonged period, as well as controlled biodegradation of the nanofiber sheets over a defined treatment period. The chapter 3 focuses on development of cross-linked electrospun cartilage acellular matrix (CAM)/poly(caprolactone-co-lactide-co-glycolide) nanofiber (Cx-CA/P-NF) with a tunable degradation period as an antiadhesive barrier. In this work, we chose CAM as a promising antiadhesive material because CAM excellently inhibits the formation of blood vessels, and we used electrospinning to prepare antiadhesive barriers. Cx-CA/P-NFs implanted between a surgically damaged peritoneal wall and cecum gradually degraded in 7 days. Additionally, the in vivo evaluation of the anti–tissue adhesion effect of Cx-CA/P-NFs revealed little adhesion, few blood vessels, and negligible necrosis at 7 days judging by histological analysis. Therefore, it is reasonable to conclude that the Cx-CA/P-NF designed herein successfully works as an anti-adhesion barrier with a tunable degradation period. In conclusion, electrospun nanofiber sheets of synthetic and natural materials have been successfully fabricated, and confirmed its biomedical applicability as drug carrier and anti-adhesion barrier.

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목차

CHAPTER 1. General introduction 1
1.1. Biomaterials 1
1.1.1. Natural materials 1
1.1.2. Synthetic materials 2
1.2. Electrospinning 3
1.2.1. Nanofibers 3
1.2.2. Applications 4
CHAPTER 2. Preparation and evaluation of dexamethasone-loaded electrospun nanofiber sheets as a sustained drug delivery system 6
2.1. Introduction 6
2.2. Materials and Methods 10
2.3. Results and Discussion 16
2.4. Conclusion 34
CHAPTER 3. Preparation of cross-linked electrospun cartilage acellular matrix/poly(caprolactone-co-lactide-co-glycolide) nanofiber and investigation of the usefulness as an antiadhesive barrier 35
3.1. Introduction 35
3.2. Experimental section 40
3.3. Results 58
3.4. Discussion 82
3.5. Conclusion 84
CHAPTER 4. Overall conclusion 85
REFERENCE 86
ABSTRACT (IN KOREAN) 101

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