title: Development of a robust pH-sensitive polyelectrolyte ionomer complex for anticancer nanocarriers.
abstract: A polyelectrolyte ionomer complex (PIC) composed of cationic and anionic polymers was developed for nanomedical applications. Here, a poly(ethylene glycol)-poly(lactic acid)-poly(ethylene imine) triblock copolymer (PEG-PLA-PEI) and a poly(aspartic acid) (P[Asp]) homopolymer were synthesized. These polyelectrolytes formed stable aggregates through electrostatic interactions between the cationic PEI and the anionic P(Asp) blocks. In particular, the addition of a hydrophobic PLA and a hydrophilic PEG to triblock copolyelectrolytes provided colloidal aggregation stability by forming a tight hydrophobic core and steric hindrance on the surface of PIC, respectively. The PIC showed different particle sizes and zeta potentials depending on the ratio of cationic PEI and anionic P(Asp) blocks (C/A ratio). The doxorubicin (dox)-loaded PIC, prepared with a C/A ratio of 8, demonstrated pH-dependent behavior by the deprotonation/protonation of polyelectrolyte blocks. The drug release and the cytotoxicity of the dox-loaded PIC (C/A ratio: 8) increased under acidic conditions compared with physiological pH, due to the destabilization of the formation of the electrostatic core. In vivo animal imaging revealed that the prepared PIC accumulated at the targeted tumor site for 24 hours. Therefore, the prepared pH-sensitive PIC could have considerable potential as a nanomedicinal platform for anticancer therapy.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, South Korea; Department of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, South Korea.
authors.forename: Chaemin
authors.initials: C
authors.lastname: Lim
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Sungkyunkwan University, Suwon, South Korea; Department of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, South Korea.
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, South Korea.
authors.forename: Kyung Soo
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, South Korea.
authors.forename: Ngoc Ha
authors.initials: NH
authors.lastname: Hoang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, South Korea.
authors.forename: Taehoon
authors.initials: T
authors.lastname: Sim
authors.affiliation: Division of Biotechnology, The Catholic University of Korea, Gyeonggi-do, South Korea.
authors.forename: Eun Seong
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, South Korea.
authors.forename: Kyung Taek
authors.initials: KT
authors.lastname: Oh
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007097:Imines / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011095:Polyethylenes / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D055672:Static Electricity; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D007097:Imines; D008823:Micelles; D011095:Polyethylenes; D011108:Polymers; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; C505405:poly(ethylene imine); D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: PEG-PLA-PEI; animal imaging; nanomedicine; pH-sensitive; polyelectrolyte ionomer complex