title: Bio-derived poly(gamma-glutamic acid) nanogels as controlled anticancer drug delivery carriers.
abstract: We have developed a novel type of polymer nanogel loaded with anticancer drug based on bio-derived poly(gamma- glutamic acid) (gamma-PGA). gamma-PGA is a highly anionic polymer that is synthesized naturally by microbial species, most prominently in various bacilli, and has been shown to have excellent biocompatibility. Thiolated gamma-PGA was synthesized by covalent coupling between the carboxyl groups of gamma-PGA and the primary amine group of cysteamine. Doxorubicin (Dox)-loaded gamma-PGA nanogels were fabricated using the following steps: (1) an ionic nanocomplex was formed between thiolated gamma-PGA as the negative charge component, and Dox as the positive charge component; (2) addition of poly(ethylene glycol) (PEG) induced hydrogen-bond interactions between thiol groups of thiolated gamma-PGA and hydroxyl groups of PEG, resulting in the nanocomplex; and (3) disulfide crosslinked gamma-PGA nanogels were fabricated by ultrasonication. The average size and surface charge of Dox-loaded disulfide cross-linked gamma-PGA nanogels in aqueous solution were 136.3 +/- 37.6 nm and -32.5 +/- 5.3 mV, respectively. The loading amount of Dox was approximately 38.7 microgram per mg of gamma-PGA nanogel. The Dox-loaded disulfide cross-linked gamma-PGA nanogels showed controlled drug release behavior in the presence of reducing agents, glutathione (GSH) (1- 10 mM). Through fluorescence microscopy and FACS, the cellular uptake of gamma-PGA nanogels into breast cancer cells (MCF-7) was analyzed. The cytotoxic effect was evaluated using the MTT assay and was determined to be dependent on both the concentration and treatment time of gamma-PGA nanogels. The bio-derived gamma-PGA nanogels are expected to be a well-designed delivery carrier for controlled drug delivery applications.
authors.affiliation: Graduate School and Department of Analytical Science and Technology, Chungnam National University, Yuseong-gu, Daejeon, Korea.
authors.forename: Hee Ho
authors.initials: HH
authors.lastname: Bae
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Cho
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Hong
authors.forename: Haryoung
authors.initials: H
authors.lastname: Poo
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Sung
authors.forename: Yong Taik
authors.initials: YT
authors.lastname: Lim
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D000080385:Nanogels; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D004220:Disulfides; D004337:Drug Carriers; D000080385:Nanogels; C511775:poly(gamma-glutamic acid); C413692:polyethylene glycol polyethyleneimine nanogel; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin; D011094:Polyethyleneimine; D005978:Glutathione