Mandracchia Delia, Rosato Antonio, Trapani Adriana, Chlapanidas Theodora, Montagner Isabella Monia, Perteghella Sara, Di Franco Cinzia, Torre Maria Luisa, Trapani Giuseppe, Tripodo Giuseppe
Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Nanomedicine. 2017 Apr;13(3):1245-1254. doi: 10.1016/j.nano.2017.01.001. Epub 2017 Jan 20.
Here, long-circulating behaviors of Inulin-based nanomicelles are demonstrated for the first time in vivo. We show the synthesis and evaluation of biotin (BIO)-decorated polymeric INVITE micelles constituted of substances of natural origin, Inulin (INU) and Vitamin E (VITE), as long-circulating carriers for receptor-mediated targeted drug delivery. The resulting INVITE or INVITE-BIO micelles, nanometrically sized, did not reveal any cytotoxicity after 24h of incubation with Caco-2 cells. Moreover, in vitro studies on Caco-2 cells monolayers indicated that the transport of INVITE-BIO micelles was faster than surface unmodified INVITE micelles. In vivo optical imaging studies evidenced that, upon intravenous administration, INVITE-BIO micelles were quantitatively present in the body up to 48h. Instead, after oral administration, the micelles were not found in the systemic circulation but eliminated with the normal intestinal content. In conclusion, INVITE-BIO micelles may enhance drug accumulation in tumor-cells over-expressing the receptor for biotin through receptor mediated endocytosis.
在此，首次在体内证明了基于菊粉的纳米胶束的长循环行为。我们展示了由天然来源的物质菊粉（INU）和维生素E（VITE）构成的生物素（BIO）修饰的聚合物INVITE胶束的合成与评估，作为用于受体介导的靶向药物递送的长循环载体。所得的纳米尺寸的INVITE或INVITE - BIO胶束在与Caco - 2细胞孵育24小时后未显示出任何细胞毒性。此外，对Caco - 2细胞单层的体外研究表明，INVITE - BIO胶束的转运比表面未修饰的INVITE胶束更快。体内光学成像研究证明，静脉给药后，INVITE - BIO胶束在体内定量存在长达48小时。相反，口服给药后，在体循环中未发现胶束，而是随正常肠道内容物排出。总之，INVITE - BIO胶束可通过受体介导的内吞作用增强药物在过表达生物素受体的肿瘤细胞中的积累。
