State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
Int J Pharm. 2013 Apr 15;447(1-2):281-92. doi: 10.1016/j.ijpharm.2013.01.068. Epub 2013 Feb 7.
The objective of the present work was to investigate the optimum density of octreotide on the surface of nanostructured lipid carriers (NLC) loaded with hydroxycamptothencine (HCPT) to enhance receptor-mediated endocytosis and tumor targeting selectivity. Different amounts of octreotide-polyethylene glycol (100) monostearate (OPMS), a ligand for somatostatin receptors (SSTRs), were coupled into NLC. In vitro evaluation of OPMS modified NLCs (O-NLCs) was done by studying the physicochemical properties, drug release, cellular uptake and cytotoxicity. Whereas in vivo evaluation was done by studying the tissue distribution in S180 tumor-bearing mice through ex vivo fluorescence imaging and HCPT quantitative study. The results showed that O-NLCs with an average size of ∼100 nm possessed obvious sustained release. When OPMS was used in the amount of 5 μmol (O₅-NLC) highest cellular uptake, cytotoxicity in SMMC-7721 cell line and remarkable accumulation in S180 tumor were observed. The treatments of O₅-NLC brought about significant tumor inhibition and prolonged the median survival time as compared with HCPT, unmodified NLC and the pegylated NLC (P₅-NLC) groups. It appears that to achieve a more rational approach of receptor mediated tumor targeted drug delivery system the surface density of the targeting moiety on the surface of nanocarriers should be considered.
本工作旨在研究载羟基喜树碱（HCPT）的纳米结构脂质载体（NLC）表面奥曲肽的最佳密度，以增强受体介导的内吞作用和肿瘤靶向选择性。将不同量的奥曲肽-聚乙二醇（100）单硬脂酸酯（OPMS），一种生长抑素受体（SSTRs）的配体，偶联到 NLC 上。通过研究物理化学性质、药物释放、细胞摄取和细胞毒性，对 OPMS 修饰的 NLC（O-NLC）进行体外评价。而通过在 S180 荷瘤小鼠中进行离体荧光成像和 HCPT 定量研究来进行体内评价。结果表明，平均粒径约为 100nm 的 O-NLC 具有明显的持续释放。当 OPMS 的用量为 5μmol（O5-NLC）时，观察到最高的细胞摄取率、SMMC-7721 细胞系的细胞毒性和 S180 肿瘤中的显著积聚。与 HCPT、未修饰的 NLC 和聚乙二醇化的 NLC（P5-NLC）组相比，O5-NLC 的治疗导致肿瘤显著抑制和中位生存时间延长。似乎为了实现更合理的受体介导的肿瘤靶向药物传递系统方法，应该考虑靶向部分在纳米载体表面的表面密度。
