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: burst release; chitosan/alginate; layer by layer; multilayer growth influencing factors; pH-dependent; poly(lactic-co-glycolic acid) nanoparticles.