Drug targeting by block copolymer micelle having targeting moiety

聚合物胶束在药物释放系统中具有重要的地位。事实上，由于其小尺寸、表观稳定性和药物溶解能力，可以认为这样的载体接近天然载体如病毒。由α-甲氧基PEO/PBLA嵌段共聚物形成的聚合物胶束已经给出了令人感兴趣的结果（小直径，约20 nm;稳定性;抗癌药物溶解的可能性，例如阿霉素）。除了通过包埋在载体中来减少抗癌药物的副作用之外，能够选择性地识别其目标的智能材料的制备也是令人感兴趣的。为此，合成在其外壳上具有官能团（如羟基）的胶束是必要的。本课题以PEO/PBLA嵌段共聚物为研究对象，对嵌段共聚物的合成、聚合物胶束的合成和表征进行了研究，并对嵌段共聚物的稳定性进行了表征，结果表明，嵌段共聚物的稳定性和稳定性均优于嵌段共聚物，嵌段共聚物的稳定性和稳定性均优于嵌段共聚物。 ...更多信息 聚合物胶束在血液中的性质与它们在肿瘤中的增强积累密切相关。与游离阿霉素（肿瘤/肌肉比=1.5）相比，聚合物胶束（肿瘤/肌肉比=40）在24小时时肿瘤与正常组织（肌肉）的蓄积比显示出数量级增加。对于形成胶束的缀合物，肿瘤对心脏的蓄积比的增加也是显著的，表明缀合物系统中心脏毒性的发生率低。偶联物在肿瘤部位的蓄积（可能通过直接外渗）可能是由于增强的血管通透性和肿瘤中的滞留效应（称为EPR效应）。为了以足够的水平实现这种效果，重要的是强调胶束的核-壳结构，以抑制胶束的疏水核与生物组分（例如，RES）通过用水合外壳覆盖核心，这将提供胶束结构在血液中的更高稳定性。少

The polymeric micelles have an important place in the field of drug delivery systems. Indeed, such carriers can be considered to bo close to natural carriers such as viruses because of their small size, apparent stability and capacity for drug solubilization. The polymeric micelles formed by alpha-methoxy PEO/PBLA blck-copolymers already gave interesting results (small diameter, c.a.20nm ; stability ; possibility of anti-cancer drug solubilization, Adriamycin for example). Besides the fact of decreasing the side effects of anti-cancer drugs by entrapment in a carrier, the preparation of intelligent materials which are able to recognize selectively their objective is of interest. For this purpose, the synthesis of micelles having functional groups (such as hydroxy groups) on their outer-shell is necessary. In this project, we conducted the synthesis of heterobifunctional PEO/PBLA block-copolymers as well as the synthesis and chariacterzation of the resulting polymeric micelles.The stabi … More lity of polymeric micelles in blood is strongly correlated with their enhanced accumulation in tumors. Tumor accumulation ratios to normal tissue (muscle) at 24 hours for polymeric micelles (tumor/muscle ratio=40) showed an order of magnitude increase in comparison to free adriamycin (tumor/muscle ratio=1.5). An increase in the tumor accumulation ratio to the heart was also significant for the micelle-forming conjugate, suggesting a low incidence of cardiac toxicity in the conjugate system. Accumulation of the conjugate at tumor sites, possibly throughdirect extravasation, might be due to enhanced vascular permeability and retention effects in a tumor, known as the EPR effect. To achieve this effect at a sufficient level, it will be important to emphasize the core-shell structure of the micelle in order to inhibit nonspecific intertactions of the hydrophobic core of the micelle with the biocomponents (e.g., RES) by covering the core with a hydrated outer shell which will provide higher stability of the micelle structure in blood. Less