PLGA-Peg-Based pH Sensitive Nanoparticles for Targeted and Controlled Drug Delivery: In Vitro Evaluation

PLGA-PEG-Based pH Sensitive Nanoparticles for Targeted and Controlled Drug Delivery: In Vitro Evaluation

 Zilan Zhou, Apurva Badkas, and Joo-Youp Lee

Chemical Engineering Program

Department of Biomedical, Chemical, and Environmental Engineering

University of Cincinnati, Cincinnati, Ohio 45221-0012

In this study, we built a drug delivery system for targeted and controlled drug delivery, which composes both active targeting abilities against HER-2 overexpressed breast cancer cells and pH response to an acidic environment inside and outside the tumor cells. A bi-functional tri-block copolymer, Poly(lactic-co-glycolic acid)-block-poly(L-histidine)-block-poly(ethylene glycol)-azide, (PLGA-Phis-PEG-N₃) was prepared and used for the construction of nanoparticles via nanoprecipitation. This tri-block copolymer contained two features.  The imidazole ring in the histidine part could be protonated or deprotonated, which endowed the tri-block copolymer with pH sensitivity.  The azide group at the end of the polymer chain was coupled with HerceptinÒ through a linker using “click chemistry” for targeted drug delivery.  

The pH responsiveness was examined for the drug release kinetics at different pH conditions as well as the particle size change. The SK-BR-3 and MCF-7 breast cancer cell lines were used to examine the efficacy of the drug delivery system. The in vitro cellular uptake of the fluorescence-labeled system was quantified using fluorometry.  The cytotoxicity of the PLGA-Phis-PEG-based nanoparticles was examined by MTS assay.