The utilization of low molecular weight heparin-poloxamer associated Laponite nanoplatform for safe and efficient tumor therapy

Abstract

In the present investigation, we have synthesized the dalteparin which is a kind of low molecular weight heparin (LMWH) and possess the antitumor and antiangiogenic efficacy with carboxylates poloxamer 407 to form a heparin-poloxamer nanogel (HP copolymer). The complex HP is capable of enhancing the efficacies, minimizing the side effects of dalteparin and exhibiting a good thermosensitivity. Therewith, the synthetic Laponite RDS (LR) nanosilicate embarked with doxorubicin (DOX) at a satisfactory high drug entrapment efficiency was integrated with the complex HP and thus constituted a newfangled biocompatible injectable temperature-sensitive hydrogel. To our delight, consociation with 2.5 w/v % of LR nanodisks, HP at the concentration of 5 w/v % was sufficient to execute the solution-gel transition at animal heat, while 17.5 w/v % of P-407 was needed for fabricating the LR-P hydrogel. Simultaneously, LR-HP possesses a more preferable syringeability. Furthermore, the release behavior in vitro for the DOX@LR-HP demonstrated as extended and controlled manner, wherein, the drug-eluting profile was regulated by the LR nanocomposites. Moreover, based on synergic action of heparin and drug, DOX@LR-HP hydrogels demonstrated the best antitumor efficacy in vitro and in vivo. What is noteworthy is that through the course of treatment, the reflected anticancer efficacy direct at the established xenograft S180 sarcoma tumor was provided by the single administration of the DOX@LR-HP hybrid gel. This excellent long-term sustainable-anticancer function in vivo demonstrating the prospect of this nanohybrid-gel combination as an estimable focal drug delivery vehicle for treatment of cancer.