Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with chitosan/alginate by layer by layer technology for antitumor applications

Fujuan Chai,1,* Linlin Sun,2,3,* Xinyi He,1 Jieli Li,1 Yuanfen Liu,4 Fei Xiong,5 Liang Ge,1 Thomas J Webster,2,3 Chunli Zheng1 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 2Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 4Department of Pharmacy, Jiangsu Jiankang Vocational College, 5State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Natural polyelectrolyte multilayers of chitosan (CHI) and alginate (ALG) were alternately deposited on doxorubicin (DOX)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) with layer by layer self-assembly to control drug release for antitumor activity. Numerous factors which influenced the multilayer growth on nano-colloidal particles were studied: polyelectrolyte concentration, NaCl concentration and temperature. Then the growth regime of the CHI/ALG multilayers was elucidated. The coated NPs were characterized by transmission electron microscopy, atomic force microscopy, X-ray diffraction and a zeta potential analyzer. In vitro studies demonstrated an undesirable initial burst release of DOX-loaded PLGA NPs (DOX-PLGA NPs), which was relieved from 55.12% to 5.78% through the use of the layer by layer technique. The release of DOX increased more than 40% as the pH of media decreased from 7.4 to 5.0. More importantly, DOX-PLGA (CHI/ALG)3 NPs had superior in vivo tumor inhibition rates at 83.17% and decreased toxicity, compared with DOX-PLGA NPs and DOX in solution. Thus, the presently formulated PLGA-polyelectrolyte NPs have strong potential applications for numerous controlled anticancer drug release applications. Keywords: layer by layer, chitosan/alginate, poly(lactic-co-glycolic acid) nanoparticles, multilayer growth influencing factors, burst release, pH-dependen