Yadav Awesh Kumar, Mishra Pradeep, Jain Sanyog, Mishra Pushpa, Mishra Anil K, Agrawal G P
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr Hari Singh Gour University, Sagar, MP, India.
J Drug Target. 2008 Jul;16(6):464-78. doi: 10.1080/10611860802095494.
The objective of the present study was to synthesize core-corona nanoparticles of doxorubicin (DOX) using hyaluronic acid-polyethyleneglycol-polycaprolactone (HA-PEG-PCL) copolymer for tumor targeting. Targeting efficiency of HA-PEG-PCL nanoparticles was compared with non-HA-containing nanoparticles (methoxy poly ethylene glycol (MPEG)-PCL). The copolymers were chemically synthesized and characterized by IR and NMR spectroscopies. The nanoparticles were characterized for shape and morphology by transmission electron microscopy, particle size, percentage of drug entrapment, and in vitro drug release profile. Differential scanning calorimetry and X-ray diffraction studies were also performed to appraise the crystalline or amorphous nature of DOX inside the polymer matrix. Formulations were prepared using different DOX:polymer ratios (1:1-1:3 w/w) and the optimum formulation with the drug:polymer ratio of 1:1 showed the mean particle size of 95 +/- 5 nm and entrapment efficiency of 95.56% in the case of HA-PEG-PCL nanoparticles, while the values were 115 nm and 95.50%, respectively, in the case of MPEG-PCL nanoparticles. The HA-PEG-PCL nanoparticles could release DOX for up to 17 days, whereas the MPEG-PCL nanoparticles could release it for up to 14 days. The hemolytic toxicity and hematological studies confirmed that both DOX-loaded HA-PEG-PCL and MPEG-PCL nanoparticles were safe and suitable for sustained and targeted drug delivery. The tissue distribution study and tumor growth inhibition were performed after intravenous injection of nanoparticles in Ehrlich ascites tumor (EAT)-bearing mice. The nanoparticles of HA-PEG-PCL copolymer accomplishes efficient delivery of DOX in EAT tumor when compared with the MPEG-PCL nanoparticles by the process of receptor-mediated endocytosis, as well as enhanced permeability and retention effect.
本研究的目的是使用透明质酸-聚乙二醇-聚己内酯（HA-PEG-PCL）共聚物合成阿霉素（DOX）的核-壳纳米颗粒，用于肿瘤靶向治疗。将HA-PEG-PCL纳米颗粒的靶向效率与不含HA的纳米颗粒（甲氧基聚乙二醇（MPEG）-PCL）进行比较。通过化学合成共聚物，并通过红外光谱和核磁共振光谱对其进行表征。通过透射电子显微镜对纳米颗粒的形状和形态、粒径、药物包封率和体外药物释放曲线进行表征。还进行了差示扫描量热法和X射线衍射研究，以评估聚合物基质内DOX的结晶或无定形性质。使用不同的DOX:聚合物比例（1:1-1:3 w/w）制备制剂，药物:聚合物比例为1:1的最佳制剂在HA-PEG-PCL纳米颗粒情况下的平均粒径为95±5 nm，包封效率为95.56%，而在MPEG-PCL纳米颗粒情况下，这些值分别为115 nm和95.50%。HA-PEG-PCL纳米颗粒可释放DOX长达17天，而MPEG-PCL纳米颗粒可释放长达14天。溶血毒性和血液学研究证实，负载DOX的HA-PEG-PCL和MPEG-PCL纳米颗粒都是安全的，适用于持续和靶向药物递送。在给荷艾氏腹水瘤（EAT）小鼠静脉注射纳米颗粒后进行组织分布研究和肿瘤生长抑制实验。与MPEG-PCL纳米颗粒相比，HA-PEG-PCL共聚物纳米颗粒通过受体介导的内吞作用以及增强的渗透和滞留效应，实现了DOX在EAT肿瘤中的有效递送。
