Institut Européen des Membranes, IEM UMR 5635, Univ Montpellier, CNRS, ENSCM, Montpellier, France.
Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Curie-Sklodowska 34 St., 41-819 Zabrze, Poland.
Int J Biol Macromol. 2020 Jul 1;154:39-47. doi: 10.1016/j.ijbiomac.2020.03.094. Epub 2020 Mar 12.
Fully bio-based amphiphilic diblock copolymers were synthesized from hydroxypropyl methyl cellulose (HPMC) and amino-terminated poly(l-lactide) (PLLA) or poly(l-lactide-co-dl-lactide) (PLA) by reductive amination. The resulting HPMC-PLLA and HPMC-PLA copolymers with various hydrophobic block lengths were characterized by NMR, DOSY-NMR and FT-IR. Micelles were obtained by self-assembly of copolymers in aqueous medium. The micelles are spherical in shape, and the micelle size ranges from 150 to 180 nm with narrow distribution. The critical micelle concentration decreases with increasing PLA block length. Paclitaxel was loaded in micelles. Enhanced drug loading is obtained with increase of PLA block length. A biphasic release profile is observed with a burst of 40% followed by slower release up to 80%. MTT assay indicates the good cytocompatibility of HPMC-PLA micelles. SRB assay shows a significant cytotoxicity of paclitaxel-loaded micelles against SK-BR-3cells. It is thus concluded that bio-based HPMC-PLA block copolymers could be promising nano-carrier of anti-tumor drugs.
全生物基两亲性嵌段共聚物由羟丙基甲基纤维素（HPMC）和端氨基聚（L-丙交酯）（PLLA）或聚（L-丙交酯-co-DL-丙交酯）（PLA）通过还原胺化反应合成。用 NMR、DOSY-NMR 和 FT-IR 对具有不同疏水性嵌段长度的所得 HPMC-PLLA 和 HPMC-PLA 共聚物进行了表征。共聚物在水介质中自组装形成胶束。胶束呈球形，粒径分布在 150-180nm 之间，分布较窄。临界胶束浓度随 PLA 嵌段长度的增加而降低。紫杉醇被载入胶束中。随着 PLA 嵌段长度的增加，药物载量增加。观察到两相释放曲线，最初释放 40%，然后缓慢释放至 80%。MTT 测定表明 HPMC-PLA 胶束具有良好的细胞相容性。SRB 测定表明紫杉醇负载胶束对 SK-BR-3 细胞具有显著的细胞毒性。因此，基于生物的 HPMC-PLA 嵌段共聚物可能是抗肿瘤药物的有前途的纳米载体。
