Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo, 105-8012, Japan.
Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama-shi, Kanagawa, 223-8522, Japan.
Colloids Surf B Biointerfaces. 2019 Apr 1;176:309-316. doi: 10.1016/j.colsurfb.2019.01.007. Epub 2019 Jan 3.
Liposomes composed of egg phosphatidylcholine and cholesterol were modified with the temperature-responsive polymer poly(N-isopropylacrylamide-co-N, N-dimethylacrylamide) (P(NIPAAm-co-DMAAm)), and exhibited reversible surface properties with temperature. Completely reversible liposome aggregation due to P(NIPAAm-co-DMAAm) hydration/dehydration was demonstrated over four successive cycles of heating and cooling. The P(NIPAAm-co-DMAAm) polymer was hydrated during cooling, which dispersed the liposomes. The rigidity of the liposomal membrane was one of the factors in the reversible aggregation, as was the modification density of the polymer on the liposomes. A low density on relatively rigid liposomes could maintain the polymer property of reversible hydrated layers below critical solution temperature (LCST) boundary. Above the LCST, temperature-responsive polymers could also transport negatively charged liposomes into cells. The reversible behavior of the temperature-responsive polymer-modified liposomes has not been reported previously and could enable new applications for switching deposit forms as alternative drug carriers.
由卵磷酯和胆固醇组成的脂质体用温度响应聚合物聚(N-异丙基丙烯酰胺-co-N,N-二甲基丙烯酰胺)(P(NIPAAm-co-DMAAm))进行了修饰,并且表现出随温度可逆的表面性质。通过加热和冷却的四个连续循环,证明了完全可逆的由于 P(NIPAAm-co-DMAAm)水合/去水合而导致的脂质体聚集。在冷却过程中,P(NIPAAm-co-DMAAm)聚合物水合,从而分散了脂质体。脂质体膜的刚性是可逆聚集的因素之一,聚合物在脂质体上的修饰密度也是因素之一。在相对刚性的脂质体上低密度可以保持低于临界溶液温度(LCST)边界的聚合物的可逆水合层的性质。在 LCST 以上,温度响应聚合物还可以将带负电荷的脂质体输送到细胞中。以前没有报道过温度响应聚合物修饰的脂质体的这种可逆行为,它可以为作为替代药物载体的沉积形式的切换提供新的应用。