Thermosensitive Poly(aspartic acid) Derivatives

Abstract

친수성인 poly(ethylene glycol)s와 소수성인 phenylalanine ethyl esters로 구성된 온도 민감성 polypeptide (아미노산 다중 결합물)을 합성하였다. 이 고분자는 대부분의 용매에서 용해가 되며, 온도가 증가함에 따라 물 상에서 micelle (radius ? 10 nm)에서 nanoparticle (radius ? 100 nm)로의 전이가 일어난다. Poly(ethylene glycol)의 graft된 수에 따라 30~40 ℃ 사이 전이온도 조절이 가능하다. ;Poly(propylene glycol)에 poly(aspartic acid)를 graft시켜 (PA-g-PPG) 생분해 pH-온도 민감성 고분자를 합성하였다. 이 고분자는 pH에 따라 LCST가 달라지며 pH를 7.4로 고정시킨 수용액 상일 경우에는 28 wt. % 이상의 농도 영역에서 온도를 증가 시킴에 따라 sol-to-gel의 전이를 보인다. 30~45 ℃에서 뭉쳐 가라앉는 현상 없이 gel상태가 유지되며 이는 PA-g-PPG의 의약전달 시스템과 조직 공학에서의 유용함을 보여준다 할 수 있다.;We designed poly(ethylene glycol) derivatives of polypeptide to introduce thermosensitivity to the polypeptide. The PEG-PP aqueous solution showed a lower critical solution temperature (LCST). By controlling the ratio of the hydrophilic PEG to the hydrophobic Phe group, transition temperature of the PEG-PP could be controlled to 30 ~ 40 oC. The higher the number of hydrophilic PEG grafts, the higher the LCST of the PEG-PP aqueous solution. Dynamic light scattering shows the PEG-PPs form micelles in water with an average radius of 10 nm below LCST. Interestingly, the precipitated PEG-PPs form nanoparticles with an average radius of 100 nm above LCST. The nanoparticles were not aggregated, but existed as a stable colloidal suspension. The nanoparticle formation at above LCST suggests the possibility of solvent-free nanoparticle preparation for hydrophobic drug delivery. The transition of nanoparticle to micelle solution was reversible.;A biodegradable pH/temperature sensitive polymer of poly(aspartic acid) grafted with poly(propylene glycol) (PA-g-PPG) was prepared. The polymer showed lower critical solution temperature (LCST) in water depending on pH. The concentrated aqueous solution of PA-g-PPG (> 28 wt. %) underwent sol-to-gel transition as the temperature increases at pH=7.4. The gel phase persisted over 30 ~ 45 ℃ without syneresis. This indicates that PA-g-PPG is a promising material for drug delivery and tissue engineering.