Polymeric complex micelles with double drug-loading strategies for folate-mediated paclitaxel delivery

Drug loading is a key procedure in the preparation of drug-loaded nano-carriers. In this study, the paclitaxel (PTX)-loaded polymeric complex micelles (FA-P123-PTX/PTX micelles) with double drug-loading strategies were designed and prepared to improve the drug loading percentage of carriers and its antitumor efficiency. PTX was simultaneously conjugated to pluronic P123 (P123) polymer and encapsulated inside the P123 complex micelle. Folate (FA) was linked to the surface of micelles for the active target delivery of micelles to tumor cells. The FA-P123-PTX/PTX micelles showed spherical shaped with high drug loading of 18.08 +/- 0.64%. The results of cellular uptake studies suggested that FA could promote the internalization of micelles into the FR positive cells. FA-P123-PTX/PTX micelles showed significant higher anti-tumor activity against FR positive tumor cells compared to Taxol (R) (p<0.05). Moreover, the FA-P123-PTX/PTX micelles exhibited higher anti-tumor efficacy in B16 bearing mice with better safety property compared with Taxol (R). These results suggested that FA-P123-PTX/PTX micelles with double drug-loading strategies showed great potential for targeted delivery of anti-cancer drugs. (C) 2015 Elsevier B.V. All rights reserved.