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Nanotubes were prepared by self-assembly of the copolymer using co-solvent evaporation method. The biocompatibility of the nanotubes was assessed in comparison with spherical micelles and filomicelles prepared from poly(ethylene glycol)-poly(L-lactide-co-glycolide) (PEG-PLGA) and poly(ethylene glycol)-poly(L-lactide) (PEG-PLA), respectively. Several aspects of biocompatibility of the aggregates were considered, including agar diffusion and MTT assay, release of cytokines, hemolysis, protein adsorption, dynamic clotting in vitro , and Zebrafish embryonic compatibility in vivo . The nanotubes present good cell compatibility and blood compatibility in vitro , and almost no toxicity towards Zebrafish embryos developmen in vivo . Furthermore, dual-loading of hydrophilic cisplatin and hydrophobic paclitaxel was achieved in the nanotubes with high loading content and loading efficiency. The release of both drugs was slower from dual-loaded nanotubes than from single-loaded ones, but the total amount of released drugs in higher for dual-loaded nanotubes than from single-loaded ones. Cellular uptake and inhibition tests showed that the nanotubes were successfully taken up by tumor cells and effectively inhibited cell growth. It is thus concluded that PEG-PLA-PEG nanotubes with outstanding biocompatibility could be promising for co-delivery of hydrophilic and hydrophobic agents in combination cancer therapy.

saudi pharmaceutical journal

Biocompatibility and paclitaxel/cisplatin dual-loading of nanotubes prepared from poly(ethylene glycol)-polylactide-poly(ethylene glycol) triblock copolymers for combination cancer therapy