Synthesis and characterization of polyethyleneimine modified methylcellulose nanocarrier for doxorubicin delivery

Methylcellulose, a cellulose ether derivative with enhanced water solubility and viscosity properties, was modified with three different molecular weights of polyethyleneimine (PEI) (0.8 k, 1.2 k, and 2 k) to synthesize cationic methylcellulose derivatives (MC–PEI). The MC–PEI derivatives exhibited varying conjugation ratios depending on the molecular weight of PEI and demonstrated significantly higher loading efficiencies for the hydrophobic drug, doxorubicin, compared to unmodified MC. The DOX@MC–PEI nanoparticles showed particle sizes ranging from 120 to 160 nm and surface charges between + 26 and + 36 mV. The drug release profiles demonstrated that MC-PEI0.8 k exhibited the highest release rate, followed by MC-PEI1.2 k and MC-PEI2k, respectively. Cytotoxicity evaluations in A549 and MDA-MB-231 cell lines revealed that MC–PEI derivatives possessed higher toxicity than MC but lower toxicity than PEI25k. In addition, the DOX@MC–PEI nanoparticles showed enhanced anticancer effects both in A549 and MDA-MB-231 cells, in particular, DOX@MC-PEI1.2k and DOX@MC-PEI2k nanoparticles showed an increased anticancer effect in MDA-MB-231 cells compared to A549 cells, which might suggest a cell-type specific DOX delivery mechanism of methylcellulose.

Graphical Abstract

Polyethyleneimine (PEI) modified methylcellulose nanocarriers (MC-PEI) were synthesized using branched PEI with three different molecular weights (0.8 kDa, 1.2 kDa, and 2 kDa). The doxorubicin-loaded nanocarriers demonstrated enhanced anticancer effects against both MDA-MB-231 and A549 cell lines