Therapeutic effects of poly(lactic acid)-poly(ethylene glycol) gel on left ventricular remodeling after myocardial infarction

心筋梗塞後左室リモデリングに対するポリ乳酸-ポリエチレングリコールゲルの治療効果

2017-09-25

2017-09-25

Suppression of left ventricular remodeling after myocardial infarction (MI) is a particularly important task in preventing heart failure. It has recently been reported that gel injection treatment is effective for improved MI. Several gel materials have been suggesting that the elastic modulus and gelation rate of the gels are important factors for attaining a good therapeutic effect. It has been difficult however to prepare such a gel that can control the strength, gelation rate, and gel degradation from biopolymers. Here, both enantiomeric multi-block copolymers, poly(L-lactic acid)-multi-poly(ethylene glycol) (PLLA-PEG) and poly(D-lactic acid)-multi- poly(ethylene glycol) (PDLA-PEG), were synthesized, and their mixed gels were prepared by thermos-responsive sol-gel transition occurring with the stereocomplex formation as the cross-linking points. The gel systems of therapeutic effect was investigated in a rat MI model. It was found out that the injection of the PLLA-PEG/PDLA-PEG mixed gel gave a therapeutic effect comparable to or even higher than the conventional injection of an alginate gel, suggesting the efficacy of the present gels. Subsequently, similar multiblock copolymers were also synthesized by the chain extension of PLLA-PEG-PLLA and PDLA-PEG-PDLA triblock copolymers with hexamethylene diisocyanate (HMDI), and the properties of their mixed gels were characterized. In the present method, the molecular weight of the multiblock copolymers was readily controlled at a constant block ratio, and the number of blocks in the molecular chain was regulated by simply changing the quantity of HMDI reacted to obtain twelve kinds of multiblock copolymers. Then, the mixed micelles composed of these enantiomeric copolymers were prepared, and their temperature-responsive sol-gel transition was analyzed. It was found that the stereocomplex formation was responsible for the gel formation and that the gel strength and gelation rate increased with increasing the number of blocks in the copolymer. Development of sol-gel materials with controllable gel strength and gelation time can be the basis of gel therapy. Therefore, the present gel systems ought to provide a new therapeutic method that maximizes the cardiac function and make their efficacy optimum.

博士（工学）

京都工芸繊維大学

14303甲第860号

http://hdl.handle.net/10212/2436

eng

ETD

Thesis or Dissertation

Thesis