시력상실을 유발할 수 있는 치명적인 안구질환을 치료하는 방법은 안약형태나 정맥주사 등의 간접적인 접근법이 환자들에게 선호되지만 낮은 약물전달율 때문에 대부분의 안과병원에서는 주사기를 사용한 직접적인 약물전달방법을 사용하고 있다. 하지만 수백 마이크로미터 수준의 바늘 첨단부로 안구조직을 통과할 때 안구통증, 출혈, 안내염 등의 심각한 부작용을 나타낼 수 있으므로 새로운 형태의 주사기 개발이 요구되었다. 마이크로니들은 마이크로미터 수준의 미세바늘로 저 통증 약물전달을 위하여 개발되었고 최소침습형태로 약물을 전달할 수 있어서 다방면에 적용이 가능하다. 본 연구에서는 이러한 마이크로니들을 ...
시력상실을 유발할 수 있는 치명적인 안구질환을 치료하는 방법은 안약형태나 정맥주사 등의 간접적인 접근법이 환자들에게 선호되지만 낮은 약물전달율 때문에 대부분의 안과병원에서는 주사기를 사용한 직접적인 약물전달방법을 사용하고 있다. 하지만 수백 마이크로미터 수준의 바늘 첨단부로 안구조직을 통과할 때 안구통증, 출혈, 안내염 등의 심각한 부작용을 나타낼 수 있으므로 새로운 형태의 주사기 개발이 요구되었다. 마이크로니들은 마이크로미터 수준의 미세바늘로 저 통증 약물전달을 위하여 개발되었고 최소침습형태로 약물을 전달할 수 있어서 다방면에 적용이 가능하다. 본 연구에서는 이러한 마이크로니들을 안질환 치료에 응용하기 위하여 긴 길이를 충족하면서도 부러지지 않고 인체 공막을 통과하거나 안구 내 망막 같은 미세조직을 투과할 수 있는 특수한 마이크로니들의 개발이 가능한 역방향 드로잉리소그래피 기술과 이 기술을 응용한 타워마이크로니들, 그리고 아크미(ARCMI)를 개발하고 소개하고자 한다. 타워마이크로니들은 안전한 유리체강 주사를 위하여 인체 공막을 투과하여 약물을 전달하기 위하여 역방향 드로잉 리소그래피 기술로 개발되었다. 45도 베벨과 100마이크로미터 크기의 첨단부로 쉽게 인체 공막 투과가 가능하여 기존에 안과에서 사용하는 가장 작은 크기의 30게이지 바늘보다 손상을 더 줄이면서 약물을 전달하였다. 또 아크미(ARCMI)는 망막하 부분에 약물을 직접적으로 주입하기 위하여 기존 타워마이크로니들 제작기술에 커브형태를 주어 제작하였다. 커브는 평균적인 인체 공막의 곡률을 적용하였으며 이는 아크미(ARCMI)를 통한 망막하 약물 주사 시에 망막손상을 최소화 할 수 있는 최적의 형태를 가지게 만들었다. 역방향 드로잉 리소그래피 방법을 이용하여 주사기에 직접 연결된 형태의 중공형 마이크로니들의 제작이 가능하였고, 이를 통하여 각각의 안질환에 맞춤형으로 대응이 가능한 초소형 약물전달기구를 개발할 수 있었다. 따라서 타워마이크로니들 형태의 중공형 마이크로니들을 제작할 수 있는 역방향 드로잉 리소그래피는 작은 주사기가 필요한 줄기세포전달을 포함한 인체 내 약물 전달 수술에 쉽게 적용이 가능하다.
시력상실을 유발할 수 있는 치명적인 안구질환을 치료하는 방법은 안약형태나 정맥주사 등의 간접적인 접근법이 환자들에게 선호되지만 낮은 약물전달율 때문에 대부분의 안과병원에서는 주사기를 사용한 직접적인 약물전달방법을 사용하고 있다. 하지만 수백 마이크로미터 수준의 바늘 첨단부로 안구조직을 통과할 때 안구통증, 출혈, 안내염 등의 심각한 부작용을 나타낼 수 있으므로 새로운 형태의 주사기 개발이 요구되었다. 마이크로니들은 마이크로미터 수준의 미세바늘로 저 통증 약물전달을 위하여 개발되었고 최소침습형태로 약물을 전달할 수 있어서 다방면에 적용이 가능하다. 본 연구에서는 이러한 마이크로니들을 안질환 치료에 응용하기 위하여 긴 길이를 충족하면서도 부러지지 않고 인체 공막을 통과하거나 안구 내 망막 같은 미세조직을 투과할 수 있는 특수한 마이크로니들의 개발이 가능한 역방향 드로잉 리소그래피 기술과 이 기술을 응용한 타워마이크로니들, 그리고 아크미(ARCMI)를 개발하고 소개하고자 한다. 타워마이크로니들은 안전한 유리체강 주사를 위하여 인체 공막을 투과하여 약물을 전달하기 위하여 역방향 드로잉 리소그래피 기술로 개발되었다. 45도 베벨과 100마이크로미터 크기의 첨단부로 쉽게 인체 공막 투과가 가능하여 기존에 안과에서 사용하는 가장 작은 크기의 30게이지 바늘보다 손상을 더 줄이면서 약물을 전달하였다. 또 아크미(ARCMI)는 망막하 부분에 약물을 직접적으로 주입하기 위하여 기존 타워마이크로니들 제작기술에 커브형태를 주어 제작하였다. 커브는 평균적인 인체 공막의 곡률을 적용하였으며 이는 아크미(ARCMI)를 통한 망막하 약물 주사 시에 망막손상을 최소화 할 수 있는 최적의 형태를 가지게 만들었다. 역방향 드로잉 리소그래피 방법을 이용하여 주사기에 직접 연결된 형태의 중공형 마이크로니들의 제작이 가능하였고, 이를 통하여 각각의 안질환에 맞춤형으로 대응이 가능한 초소형 약물전달기구를 개발할 수 있었다. 따라서 타워마이크로니들 형태의 중공형 마이크로니들을 제작할 수 있는 역방향 드로잉 리소그래피는 작은 주사기가 필요한 줄기세포전달을 포함한 인체 내 약물 전달 수술에 쉽게 적용이 가능하다.
Serious ocular diseases resulting in irreversible blindness such as age-related macular degeneration (AMD) and diabetes retinopathy can occur due to retinal problems in the back side of the eye. Consequently, most of the pharmaceutical researcher and ophthalmologist has focused on the drug delivery ...
Serious ocular diseases resulting in irreversible blindness such as age-related macular degeneration (AMD) and diabetes retinopathy can occur due to retinal problems in the back side of the eye. Consequently, most of the pharmaceutical researcher and ophthalmologist has focused on the drug delivery towards retina in the back side of the eye to treat severe retinal diseases. Although topical and systemic administration routes have been developed for ocular drug delivery, below the five percentage of delivery efficiency due to ocular globes including sclera has been an obstacle as well as side effects in the blood stream to treat retinal disease. Therefore, the direct drug delivery using the hypodermic needle in ophthalmology have been used extensively globally during the past several decades due to a relatively high delivery efficiency of drug compared to the traditional delivery routes such as topical and systemic administration. However, ocular tissue damage induced by large diameter of hypodermic needle give rise to severe symptom such as irreversible scar, large bleb and hemorrhage. Although hypodermic needles with smallest diameter around 3 hundred microns were developed, it was not enough to reduce the damage on the eye. Microneedle, three dimensional (3D) micron scale needle-like structure, have been developed originally as an alternative to replace the hypodermic needle in transdermal drug delivery. Small diameter of microneedle tip reduce the insertion force and tissue damage of the skin. For this reason, microneedle also can be a potential alternative for traditional hypodermic needle in ophthalmology. In this study, reverse drawing lithography, a novel fabrication method of hollow microneedle for the ocular drug delivery to treat serious retinal diseases, was described as well as applications of hollow microneedle fabricated by reverse drawing lithography for intravitreal, sub-retinal and endovascular injection. Reverse drawing lithography, the unique technique to make the hollow microneedle on the blunt tip of stainless steel cannula, was developed for innocuous ocular drug delivery with long and strong hollow microneedle connected to the individual syringe concentrically. Tower microneedle (TM), a hollow microneedle, was developed via reverse drawing lithography for intravitreal injection with minimal scleral tissue damage and less reflux which was regarded as a drug loss. A traditional 30 Gauge (G) hypodermic needle was used as a control. Intravitreal delivery of real drug by tower microneedle was proven with intravitreal injection of anti-vascular endothelial growth factor antibody with Tower Microneedle. According to the result, tower microneedle can deliver the drug well into the back side of the eye by intravitreal injection with minimal tissue damage and minimal bleb formation. It can be a good alternative for hypodermic needle in intravitreal drug administration. In sub-retinal drug delivery, arched micro-injector (ARCMI) was developed by combination technology between continuous air-blowing and reverse drawing lithography to make curved hollow microneedle for sub-retinal injection. The ARCMI is characterized with curved tip in accordance with the retina curvature as well as with about hundred micrometer tip diameter. The optimization of curvature of ARCMI was performed by in-vitro experiment with artificial ocular globes and by ex-vivo experiment with sub-retinal indocyanine green injection in porcine eye. Consequently, arched micro-injector (ARCMI) for innocuous sub-retinal injection was developed with optimized specific characteristics such as 5 mm length, 0.15 mm-1 curvatures, about 100 microns outer diameter and 45° beveled tip for minimal tissue damage during sub-retinal injection. Especially, 0.15 mm-1 curvature of ARCMI was major factor to achieve minimal retinal tissue damage by fitting with human ocular curvature. According to result, ARCMI can be a good surgical tool in sub-retinal drug injection as well as retinal stem cell delivery. Conclusively, various applications of Tower Microneedle and ARCMI can be a breakthrough for safe ocular drug delivery as well as stem cell delivery.
Serious ocular diseases resulting in irreversible blindness such as age-related macular degeneration (AMD) and diabetes retinopathy can occur due to retinal problems in the back side of the eye. Consequently, most of the pharmaceutical researcher and ophthalmologist has focused on the drug delivery towards retina in the back side of the eye to treat severe retinal diseases. Although topical and systemic administration routes have been developed for ocular drug delivery, below the five percentage of delivery efficiency due to ocular globes including sclera has been an obstacle as well as side effects in the blood stream to treat retinal disease. Therefore, the direct drug delivery using the hypodermic needle in ophthalmology have been used extensively globally during the past several decades due to a relatively high delivery efficiency of drug compared to the traditional delivery routes such as topical and systemic administration. However, ocular tissue damage induced by large diameter of hypodermic needle give rise to severe symptom such as irreversible scar, large bleb and hemorrhage. Although hypodermic needles with smallest diameter around 3 hundred microns were developed, it was not enough to reduce the damage on the eye. Microneedle, three dimensional (3D) micron scale needle-like structure, have been developed originally as an alternative to replace the hypodermic needle in transdermal drug delivery. Small diameter of microneedle tip reduce the insertion force and tissue damage of the skin. For this reason, microneedle also can be a potential alternative for traditional hypodermic needle in ophthalmology. In this study, reverse drawing lithography, a novel fabrication method of hollow microneedle for the ocular drug delivery to treat serious retinal diseases, was described as well as applications of hollow microneedle fabricated by reverse drawing lithography for intravitreal, sub-retinal and endovascular injection. Reverse drawing lithography, the unique technique to make the hollow microneedle on the blunt tip of stainless steel cannula, was developed for innocuous ocular drug delivery with long and strong hollow microneedle connected to the individual syringe concentrically. Tower microneedle (TM), a hollow microneedle, was developed via reverse drawing lithography for intravitreal injection with minimal scleral tissue damage and less reflux which was regarded as a drug loss. A traditional 30 Gauge (G) hypodermic needle was used as a control. Intravitreal delivery of real drug by tower microneedle was proven with intravitreal injection of anti-vascular endothelial growth factor antibody with Tower Microneedle. According to the result, tower microneedle can deliver the drug well into the back side of the eye by intravitreal injection with minimal tissue damage and minimal bleb formation. It can be a good alternative for hypodermic needle in intravitreal drug administration. In sub-retinal drug delivery, arched micro-injector (ARCMI) was developed by combination technology between continuous air-blowing and reverse drawing lithography to make curved hollow microneedle for sub-retinal injection. The ARCMI is characterized with curved tip in accordance with the retina curvature as well as with about hundred micrometer tip diameter. The optimization of curvature of ARCMI was performed by in-vitro experiment with artificial ocular globes and by ex-vivo experiment with sub-retinal indocyanine green injection in porcine eye. Consequently, arched micro-injector (ARCMI) for innocuous sub-retinal injection was developed with optimized specific characteristics such as 5 mm length, 0.15 mm-1 curvatures, about 100 microns outer diameter and 45° beveled tip for minimal tissue damage during sub-retinal injection. Especially, 0.15 mm-1 curvature of ARCMI was major factor to achieve minimal retinal tissue damage by fitting with human ocular curvature. According to result, ARCMI can be a good surgical tool in sub-retinal drug injection as well as retinal stem cell delivery. Conclusively, various applications of Tower Microneedle and ARCMI can be a breakthrough for safe ocular drug delivery as well as stem cell delivery.
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