Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
Department of Pharmacy, University of Bari "Aldo Moro", Via Orabona 4, 70125 Bari, Italy.
Colloids Surf B Biointerfaces. 2015 Jan 1;125:300-8. doi: 10.1016/j.colsurfb.2014.11.034. Epub 2014 Dec 2.
This work reports on the formation of a carrier-in-carrier device for the systemic delivery and targeting of hydrophobic drugs mediated by micelle-loaded mesenchymal stromal cells (MSCs) (carrier-in-carrier) to be administered by intravenous injection. The innate ability of MSCs to reach injured tissues such as the central nervous system or other damaged tissues, is the key for the second order delivery and first order targeting. Inulin-D-alfa-tocopherol succinate micelles (INVITE M) are able to incorporate highly hydrophobic drugs and, due to their dimensions (≈7 nm diameter), to penetrate the cell membrane easily and quickly. This study demonstrates that the curcumin loaded micelles (INVITE MC), sterilized by filtration, reached the maximum loading in MSCs in few minutes and that the loading was concentration-dependent. When "naked" curcumin was used, an evident cytotoxicity on MSCs was detected, while INVITE micelles protected them from this effect. Moreover, MSCs loaded with INVITE MC are able to release the entrapped drug. This study strongly supports the feasibility of the carrier-in-carrier approach for the therapy of selected diseases, i.e., this innovative drug delivery system will be proposed for the treatment of the amyotrophic lateral sclerosis (ALS).
本工作报道了一种载体-载体装置的形成，用于通过静脉注射介导的胶束负载间充质基质细胞（MSCs）（载体-载体）进行系统递药和靶向疏水性药物。MSCs 到达损伤组织（如中枢神经系统或其他受损组织）的固有能力是进行二次递药和一级靶向的关键。菊粉-D-生育酚琥珀酸酯胶束（INVITE M）能够包载高度疏水性药物，并且由于其尺寸（≈7nm 直径），能够轻松快速地穿透细胞膜。本研究表明，通过过滤灭菌的载姜黄素胶束（INVITE MC）能够在几分钟内达到 MSCs 的最大载药量，并且载药量呈浓度依赖性。当使用“裸”姜黄素时，检测到 MSCs 明显的细胞毒性，而 INVITE 胶束则保护它们免受这种影响。此外，负载有 INVITE MC 的 MSC 能够释放包封的药物。这项研究强烈支持载体-载体方法用于治疗选定疾病的可行性，即，这种创新的药物递送系统将被提议用于治疗肌萎缩侧索硬化症（ALS）。
