Doxorubicin-loaded nanoparticles consisted of cationic- and mannose-modified-albumins for dual-targeting in brain tumors

Journal of Controlled Release : Official Journal of the Controlled Release Society
Hyeong Jun ByeonYu Seok Youn

Abstract

Albumin nanoparticles have been increasingly viewed as an effective way of delivering chemotherapeutics to solid tumors. Here, we report the one-pot development of a unique prototype of doxorubicin-loaded nanoparticles (NPs) made of naïve albumin (HSA) plus cationic- (c-HSA) or mannose-modified-albumin (m-HSA), with the goal of traversing the blood-brain barrier and targeting brain tumors. c-HSA was synthesized by conjugating ethylenediamine to naïve HSA. Then, m-HSA was derivatized using mannopyranoside via a thiol-maleimide reaction. The c/m-HSA NPs were prepared using a mixture solution of c- and m-HSAs in deionized water and doxorubicin in ethanol/chloroform in the same pot using a high-pressure homogenizer. The c/m-HSA NPs were spherical and well-dispersed, with a particle size of 90.5±3.1nm and zeta-potential of -12.0±0.3mV at c- and m-HSA feed ratios of 5% and 10%, respectively. The c/m-HSA NPs displayed good stability over 3days based on particle size and a linear gradual doxorubicin release over 2days. Specifically, the inhibitory concentration (IC50; 0.5±0.02μg/ml) of c/m-HSA NPs was >2.2-15.6 fold lower than those of doxorubicin or the other HSA NPs. Moreover, among HSA NPs, c/m-HSA NPs exhibited the most prominent p...Continue Reading

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