线性的,Y形,和甲氧基聚(乙二醇)-嵌段-聚酰胺胺-嵌段-聚(1-谷氨酸)(MPEG-b-PAMAM-b-PGA)的线性树枝状嵌段共聚物,两个,四,和八个PGA臂,但相似的MPEG/PGA重量比(W/W)(称为P1PA,P2PA,P4PA和P8PA,分别)合成并比较研究了盐酸多柔比星(DOX)的递送。所有获得的嵌段共聚物都具有高度的生物相容性,并且可以通过静电相互作用将DOX有效地负载到纳米颗粒(NPs)中。由线性(P1PA)或Y形(P2PA)嵌段共聚物和DOX形成的NP为球形,尺寸较小,而由线性树枝状嵌段共聚物(P4PA和P8PA)形成的NP形状不规则且尺寸较大。P1PA/DOX和P2PA/DOXNP表现出更好的DOX保护和更慢的DOX释放曲线。然而,细胞毒性试验表明,所有负载DOX的NP都表现出与游离DOX相似的细胞毒性,表明细胞摄取后有效的DOX释放。线性和Y形嵌段共聚物的NPs大大延长了血液循环时间,与线性树突状组织相比,在肿瘤部位的积累更多,在肝脏和肾脏的积累更少。此外,与其他DOX制剂相比,P1PA/DOX和P2PA/DOXNP也表现出更高的抗肿瘤功效和更低的毒性。所有这些结果表明,线性和Y形MPEG-b-PAMAM-b-PGA嵌段共聚物在抗肿瘤治疗中显示出比线性树枝状共聚物更好的DOX递送能力。
衍生自嵌段共聚物的聚合物NP已成为药物递送的有效载体。然而,该领域的大部分研究涉及简单的线性嵌段共聚物,很少有关于自组装的比较研究,在体外,和通过具有相似组成但不同结构的嵌段共聚物的体内药物递送。在这项研究中,一系列的线性,Y形,制备和基于线性树枝状多肽的嵌段共聚物,并对DOX递送进行彻底研究。这些嵌段聚合物将DOX加载到具有不同大小和形态的NP中,并在体外和体内表现出不同的抗肿瘤能力。结果表明,嵌段共聚物的结构在其药物传递行为中起着重要作用。
The linear, Y-shaped, and linear-dendritic block copolymers of methoxy poly(ethylene glycol)-block-polyamidoamine-block-poly(l-glutamic acid) (MPEG-b-PAMAM-b-PGA) with one, two, four, and eight PGA arms but similar MPEG/PGA weight ratios (W/W) (named as P1PA, P2PA, P4PA and P8PA, respectively) were synthesized and comparatively investigated for doxorubicin hydrochloride (DOX) delivery. All the obtained block copolymers were highly biocompatible and could efficiently load DOX into nanoparticles (NPs) through electrostatic interaction. The NPs formed by linear (P1PA) or Y-shaped (P2PA) block copolymers and DOX were spherically shaped with smaller sizes, while the NPs formed from linear-dendritic block copolymers (P4PA and P8PA) were irregular in shape and larger in size. The P1PA/DOX and P2PA/DOX NPs exhibited better DOX protection and slower DOX release profile. However, cell cytotoxicity assays indicated that all the DOX-loaded NPs exhibited similar cytotoxicities with free DOX, indicating effective DOX release after cellular uptake. The NPs from linear and Y-shaped block copolymers greatly extended the blood circulation time, and displayed more accumulation in tumor site and less accumulation in the liver and kidney compared with the linear-dendritic counterparts. In addition, the P1PA/DOX and P2PA/DOX NPs also exhibited higher anti-tumor efficacy and less toxicity than the other DOX formulations. All these results indicated that the linear and Y-shaped MPEG-b-PAMAM-b-PGA block copolymers displayed better DOX delivery ability in anti-tumor treatment than the linear-dendritic copolymers.
Polymeric NPs derived from block copolymers have emerged as effective vehicles for drug delivery. However, the majority of the researches in this field have involved simple linear block copolymers and there are very few comparative studies on the self-assembly, in vitro, and in vivo drug delivery by the block copolymers with similar composition but different architectures. In this study, a series of linear, Y-shaped, and linear-dendritic polypeptide-based block copolymers were prepared and thoroughly investigated for DOX delivery. These block polymers loaded DOX into NPs with different sizes and morphologies, and exhibited different anti-tumor capabilities both in vitro and in vivo. The results indicated that the architecture of the block copolymers played an important role in their drug delivery behaviors.