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Radioisotope carrying polymeric microemulsion for development of diagnostic targeting device

Radioisotope carrying polymeric microemulsion for development of diagnostic targeting device
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대학원 약학과
이화여자대학교 대학원
The purpose of this research was to develop polymeric system for delivery of radioactive or therapeutic agent to target site with high accuracy and efficacy. For this purpose, microemulsions based on polyethyleneoxide(PEO) were developed. The use of PEO would be advantageous for prolongation of blood circulation, avoidance of albumin adsorption owing to hydrophilic property and chain mobility of PEO. In addition, suitable regulation of size distribution is one of the major benefit of the microemulsion as targetable devices. These microemulsions may have favorable surface property and size distribution for imaging blood vessel or bone marrow, avoiding reticuloendothelial system (RES) uptake by liver and spleen. Transparent microemulsions were prepared with PEO polymers and Transcutol^((r)). Microemulsions with Tween80^((r)) and Cremophore^((r)) revealed similar phase behaviour. However, Cremophore^((r)) showed increased microemulsion lesions at 50-70% surfactant contents. This is due to increased micelle formation in Cremophore^((r)) containing microemulsion. Microemulsion was not formed without Transcutol^((r)), however, phase diagram revealed that increased cosurfactant ratio to surfactant did not induce effective microemulsion formation. This result demonstrates that Transcutol^((r)) increased surfactant micelle mobility to certain limits and decreased micelle formation above this limit. Size of Cremophore^((r)) EL microemulsion was larger than that of Tween 80^((r)) microemulsion in the same content, sorfactant/cosurfactant ratio. Size of the microemulsion prepared with Tween 80^((r)) belonged bewteen 50-150nm, which may be adequate for long circulating and bone marow imaging. The size distribution increased as cosurfactant ratio to surfactant, oil phase. The viscosity of the microemulsions increased as surfactant content and cosurfactant ratio to surfactant increased. The microemulsions made of MAG3-, HPP- or cDTPA- conjugated polymers also had slightly increased size distribution owing to hydrophobicity of the ligands, however, it was still favorable for imagimg blood vessel and avoiding RES uptake. Therefore, microemulsions with these ligand bound PEO polymers might be a useful tool as a diagnostic targeting device and optimization of fabrication condition, it demonstrated long blood circulation and low liver RES uptake. From these results, these microemulsion systems are expected to be used as a diagnostic and treating agent for various type of disease. ;본 연구는 진단 및 치료효율을 높이기 위한 방사성 고분자 동위 원소 표지 미립자 수송체 개발에 목표를 두고 있다. 이물 탐식 기구를 피하고 혈액중에 장시간 머무르면서 혈관의 영상화와 골수로의 이행에 의한 영상화를 도모할 수 있는 표면 성질과 적절한 입자도를 가지는 미립자 제제를 개발함을 목표로 하고 있다. 각 system은 O/W microemulsion으로 제조되었다. Microemulsion의 삼상도 영역, 입자도 분포, 점도등은 surfactant의 양과 surfactant : cosurfactant와의 비에 의해 영향을 받았다. 혈액내에서 장시간 순환하면서 골수로의 이행에 적절한 크기인 50-150nm 입자도를 지니는 system을 선택하여 ligand와 결합된 polymer를 이용한 microemulsion을 제조하여 방사성 동위원소를 표지하였다. 이렇게 제조된 microemulsion은 body distribution에 의해 long blood circulation과 낮은 RES uptake를 관찰할 수 있었다. 이러한 결과들로부터 이 microemulsion system은 각종 질병의 진단 및 치료에 있어서 targeting device로써 유용성이 기대되었다.
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