Preparation and in vitro evaluation of arsenic trioxide-loaded glioma targeting drug delivery system iRGD/TGN-PEG-PAMAM/ATO / 中草药

ABSTRACT

Objective To construct a glioma targeting delivery system, PAMAM G5 were modified with the oligopeptide of blood brain barrier (BBB) targeting TGN and tumor targeting oligopeptide iRGD to solve the problem of non-specificity in distribution and difficulty in permeating BBB of ATO, in order to have better anti-glioma effect. Methods The physical and chemical properties of nanocarriers were investigated by 1H-NMR and transmission electron microscopy (TEM); The encapsulation efficiency and in vitro release were analyzed by inductively coupled plasma emission spectrum (ICP) and dialysis bag method; The effects of iRGD and TGN on cellular uptake of the carriers were analyzed by laser confocal and flow cytometry. The cytotoxicity of nanocarriers on brain microvascular endothelial cells (HBMEC) and glioma cells (U87), the inhibition effect on U87 cells of drug delivery systems after acrossing the BBB model in vitro were investigated by MTT method. Results The iRGD/TGN-PEG-PAMAM was synthesized successfully. The TEM results showed that iRGD/TGN-PEG-PAMAM was regular in shape and uniform in size. The particle size of iRGD/TGN-PEG-PAMAM/ATO was (24.87 ± 0.84) nm and the potential was (17.26 ± 1.64) mV. The synthesized carrier had less toxicity to HBMEC and U87 cells. The encapsulation efficiency of iRGD/TGN-PEG-PAMAM/ATO delivery system was (71.92 ± 1.17)%. The in vitro release showed that ATO had a slow release trend after entrapment, and it was more favorable for ATO release under acidic conditions. The cell uptake indicated that iRGD/TGN modification was more beneficial for U87 cell to uptake the drug delivery system. The in vitro inhibition effect on U87 cells after acrossing the BBB model showed iRGD/TGN-PEG-PAMAM/ATO had better inhibition effect on U87 cells. Conclusion The iRGD/TGN-PEG-PAMAM/ATO targeting drug delivery system has good inhibition effect on U87 cells effect after acrossing the BBB model in vitro, which provides a new strategy for the treatment of glioma.