Inhibition of Intimal Hyperplasia by Perivascular Delivery of Paclitaxel Using Poly(n-butylmethacrylate) or Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) in Balloon-Injured Rat Carotid Arteries

Polymer is a critical component of local drug delivery to prevent restenosis. This study tested whether poly(n-butylmethacrylate)(PBMA) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(PHA) was candidates for this purpose. In vitro release of paclitaxel from PBMA and PHA loaded with 10% paclitaxel exhibited a triphasic release profile, with a fast initial and intermediate second phase followed by a slow release phase. Perivascular delivery of paclitaxel using these films inhibited neointimal hyperplasia in balloon-injured rat carotid arteries. The paclitaxel-loaded PBMA or PHA groups showed significant neointimal formation reductions versus the control groups (PBMA vs control: $0.03{\pm}0.02$ vs $0.10{\pm}0.01\;mm^2$, p<0.05; PHA vs control: $0.04{\pm}0.03$ vs $0.09{\pm}0.01\;mm^2$, p<0.05). This study suggests that PBMA and PHA could be good candidate polymers of local drug delivery to prevent restenosis. Perivascular delivery using these films represents a possible approach for prevention of restenosis. These can be candidate polymers for drug eluting stents.

쥐 경동맥 손상 모델에서 Poly(n-butylmethacrylate) 혹은 Poly(3-hydroxybutyrate-co-4-hydroxybutyrate)를 이용한 Paclitaxel 국소 전달 요법의 신생내막 형성 억제 효과

Poly(n-butylmethacrylate)(PBMA)와 poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(PHA)가 혈관 협착 방지를 위한 국소 약물 요법시 유용한 고분자인지 검정하였다. 10% paclitaxel 함유 필름으로부터 방출되는 paclitaxel은 초기 1주간은 빠르게, 30일까지는 중증도로, 이후는 천천히 방출되었다. Paclitaxel 함유 필름들은 풍선 손상을 가한 쥐 경동맥의 신생내막 증식을 억제하였다(PBMA vs control : $0.03{\pm}0.02$ vs $0.10{\pm}0.01\;mm^2$, p<0.05; PHA vs control: $0.04{\pm}0.03$ vs $0.09{\pm}0.01\;mm^2$, p<0.05). PBMA와 PHA는 혈관 협착 방지를 위한 약물 전달 고분자로 유용할 것으로 사료된다. 고분자 필름은 혈관 외벽에 장착이 용이한 경우 사용될 수 있다. 또한, 이 고분자들은 약물 방출 스텐트 개발시 이용될 수 있다.