PEG-PLGA Nanoparticle modified by Transferrin Loading Doxorubicin: in vitro and in vivo Studies for Glioma

摘要

Purpose A biodegradable PEG-PLGA nanoparticle(NP) modified by transferrin (Tf) was conceived. Doxorubicin (Dox), a widely used antitumor agent, without passing through the BBB, which limited its utility on glioma, was encapsulated inside (Tf-NP-Dox). Furthermore, its therapeutic efficacy to glioma was evaluated both in vitro and in vivo. Methods Tf-NP-Dox was prepared via modified single emulsion method. Its characterization including size, Drug loading capacity (DLC), entrapment efficiency (EE), Tf number on Tf-NP-Dox surface were estimated. The antitumor efficiency in vitro was evaluated via MTT assay. The transmembrane transportation was evaluated via HPLC assay. The antitumor efficiency in vivo was assessed on C6 glioma intracranial implant rats model. Results: The average diameter of Tf-NP-Dox is around 200 nm with surface Tf molecule number per Tf-NP-Dox approximately 25. MTT assay demonstrated stronger cytotoxicity of Tf-NP-Dox to C6 glioma cells (P<0.01). HPLC assay showed Tf-NP-Dox transport Dox into C6 with higher efficiency compare to NP-Dox or Dox (P<0.01). On C6 glioma bearing rat, Tf-NP-Dox could transport more Dox into tumors tested by HPLC assay (P<0.05), and extended life span markedly compared to NP-Dox or Dox (P<0.05). Conclusions Tf-NP-Dox had a potential of glioma targeting and had a better therapeutic effect to glioma both in vitro and in vivo.