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Enhanced tumor delivery and antitumor response of doxorubicin loaded albumin nanoparticles formulated based on a Schiff base

Authors Li F, Zheng C, Xin J, Chen F, Ling H, Sun L, Webster TJ, Ming X, Liu J

Received 17 March 2016

Accepted for publication 8 May 2016

Published 12 August 2016 Volume 2016:11 Pages 3875—3890

DOI https://doi.org/10.2147/IJN.S108689

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 2

Editor who approved publication: Professor Carlos Rinaldi

Fang Li,1,2,* Chunli Zheng,1,* Junbo Xin,2 Fangcheng Chen,1 Hua Ling,3 Linlin Sun,4 Thomas J Webster,4,5 Xin Ming,6 Jianping Liu1

1School of Pharmacy, China Pharmaceutical University, Nanjing, 2School of Pharmacy, Yancheng Vocational Institute of Health Sciences, Yancheng, People’s Republic of China; 3School of Pharmacy, Hampton University, Hampton, VA, 4Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 5Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia; 6Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA

*These authors contributed equally to this work


Abstract: A novel method was developed here to prepare albumin-based nanoparticles (NPs) for improving the therapeutic and safety profiles of chemotherapeutic agents. This approach involved crosslinking bovine serum albumin (BSA) using a Schiff base-containing vanillin, into NPs and loading doxorubicin (DOX) into the NPs by incubation. The resultant NPs (DOX-BSA-V-NPs) displayed a particle size of 100.5±1.3 nm with a zeta potential of –23.05±1.45 mV and also showed high drug-loading efficiency and excellent stability with respect to storage and temperature. The encapsulation of DOX into the BSA-V-NPs was confirmed by dynamic scanning calorimetry and Raman spectroscopy. DOX-BSA-V-NPs exhibited a significantly faster DOX release at pH 6.5 than pH 7.4, as well as in a solution with a higher glutathione concentration. In vitro studies showed that the cellular uptake of DOX-BSA-V-NPs was time-dependent, concentration-dependent, and faster than free DOX, while the cytotoxicity of DOX-BSA-V-NPs (IC50 value of 3.693 µg/mL) was superior to free DOX (IC50 value of 4.007 µg/mL). More importantly, DOX-BSA-V-NPs showed a longer mean survival time of 24.83 days, a higher tumor inhibition rate of 56.66%, and a decreased distribution in the heart than other DOX formulations in animal studies using a tumor xenograft model. Thus, the vanillin-based albumin NPs were shown here to be a promising carrier for tumor-targeted delivery of chemotherapeutic agents and, thus, should be further studied.

Keywords: doxorubicin, albumin nanoparticles, Schiff base, tumor delivery, anticancer response

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