Article
  • Polymeric Micelle Using Poly((R)-3-hydroxybutyric acid)/ Poly(ethylene glycol) Amphiphilic Block Copolymer for Drug Delivery System
  • Jeong KH, Kim YJ
  • Poly((R)-3-hydroxybutyric acid)/Poly(ethylene glycol) 양친성 블록 공중합체를 이용한 약물전달체용 고분자 미셀
  • 정관호, 김영진
Abstract
A biodegradable polymer poly((R)-3-hydroxybutyric acid)(PHB) was conjugated with a hydrophilic polymer poly(ethylene glycol)(PEG) by the transesterification reaction to form the amphiphilic block copolymer. PHB with low molecular weight (3000∼30000) was appropriated for the drug delivery materials. High molecular weight PHB was hydrolyzed by an acid-catalyst to produce the low molecular weight one. Amphiphilic block copolymer was formed the self-assembled polymeric micelle system in the aqueous solution that the hydrophillic PEG was wraped the hydrophobic PHB. Generally, polymeric micelle forms the small particle between 10∼200 nm. These polymeric micelle systems have been widely used for the drug delivery systems because they were biodegradable, biocompatible, non-toxic and patient compliant. The hydroxyl group of PEG was substituted with carboxyl group which has the reactivity to the ester group of PHB. Amphiphilic block copolymer was conjugated between PHB, and modified PEG at 176 ℃ which was higher than the melting point of PHB. Transesterification reaction was verified with DSC, FTIR, 1H-NMR. In the aqueous solution, critical micelle concentration(CMC) of the mPEG-co-PHB copolymer measured by the fluororescence scanning spectrometer was 5×10-5 g/L. The shape and size of the nanoparticle was taken by dynamic light scattering and atomic force microscopy. The size of the nanoparticle was about 130 nm and the shape was spherical. Our polymeric micelle system can be used as the passive targeting drug delivery system.

양친성 블록공중합체는 생분해성 고분자인 poly((R)-3-hydroxybutyric acid), PHB와 친수성 고분자인 poly(ethylene glycol), PEG를 이용하여 제조되었다. 미생물에 의해 생산된 분자량이 수십만인 PHB는 약물전달용 재료로 적합하지 않으므로 산 촉매 가수분해를 통해 분자량이 3000∼30000을 가지도록 조절되었다. 공중합체를 수용액에 넣으면, 고분자들은 자기 조립에 의해 친수성인 PEG가 소수성인 PHB를 감싸는 형태의 고분자 미셀을 형성한다. 형성된 고분자 미셀은 생분해성과 생체적합성을 가지면서 생체 내에서 낮은 독성과 환자 친화적인 특성을 가지므로 약물 전달체로의 이용이 가능하다. 양친성 블록 공중합체는 PHB에 PEG를 도입한 것으로 에스테르교환(transesterification) 반응을 통해 유도되었다. PEG는 친수성 블록의 형성과 반응성을 향상시키기 위해 말단의 작용기를 개질한 후 사용되었다. 양친성 블록 공중합체 형성에 대한 열적 특성과 화학적 구조 분석은 DSC, FTIR, 1H-NMR을 사용하여 알아보았다. 임계 미셀 농도(critical micelle concentration, CMC)는 고분자 미셀이 형성되는 시점으로 형광 분광기를 사용하여 분석한 결과 5×10-5 g/L 부근에서 측정되었다. 수용액 상의 고분자 미셀은 냉동 건조 후, 분말 형태의 나노입자를 얻었다. 고분자 미셀의 크기는 dynamic light scattering으로 측정한 결과 약 130 nm 정도로 나타났다. 또한 atomic force microscopy 측정을 통해 크기가 약 130 nm 정도인 구형 입자를 확인하였다. 나노입자가 형성된 고분자 미셀은 소수성 약물을 담지하여 수동적 표적지향형 약물 전달용 수송체로 이용이 가능할 것이다.

Keywords: PHB; PEG; transesterification; polymeric micelle; drug delivery system

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  • Polymer(Korea) 폴리머
  • Frequency : Bimonthly(odd)
    ISSN 0379-153X(Print)
    ISSN 2234-8077(Online)
    Abbr. Polym. Korea
  • 2023 Impact Factor : 0.4
  • Indexed in SCIE

This Article

  • 2006; 30(6): 512-518

    Published online Nov 25, 2006

  • Received on Jul 19, 2006
  • Accepted on Sep 19, 2006