title: Lactosylated PLGA nanoparticles containing ϵ-polylysine for the sustained release and liver-targeted delivery of the negatively charged proteins.
abstract: The acidic internal pH environment, initial burst release and lack of targeting property are main limitations of poly(lactide-co-glycolide) (PLGA) nanoparticles for carrying proteins. In this study, ϵ-polylysine (ϵ-PL) was used as an anti-acidic agent and a protein protectant to prepare PLGA nanoparticles for the protein delivery. To obtain the liver-targeting capability, lactosylated PLGA (Lac-PLGA) was synthesized by conjugation of lactose acid to PLGA at both ends, and then used to prepare nanoparticles containing ϵ-PL by the nanoprecipitation method. Bovine serumal bumin (BSA), a negatively charged protein, was efficiently loaded into Lac-PLGA/ϵ-PL nanoparticles and exhibited significant decreased burst release in vitro, sustained release in the blood and increased liver distribution in mice after intravenous injections. The enhanced stability of BSA was due to its electrical interaction with ϵ-PL and the neutralized internal environment of nanoparticles. In conclusion, Lac-PLGA/ϵ-PL nanoparticle system can be used as a promising carrier for the negatively charged proteins.
authors.affiliation: Research Center of Basic Medical Science, School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Institute of Biomedical Engineering, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Research Center of Basic Medical Science, School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Institute of Biomedical Engineering, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors.forename: Tong
authors.initials: T
authors.lastname: An
authors.affiliation: Research Center of Basic Medical Science, School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Institute of Biomedical Engineering, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Research Center of Basic Medical Science, School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Institute of Biomedical Engineering, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Research Center of Basic Medical Science, School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Institute of Biomedical Engineering, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors.forename: Rongshan
authors.initials: R
authors.lastname: Li
authors.affiliation: Research Center of Basic Medical Science, School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Institute of Biomedical Engineering, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Research Center of Basic Medical Science, School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Institute of Biomedical Engineering, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China. Electronic address: wangyinsong@tijmu.edu.cn.
authors.forename: Yinsong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Research Center of Basic Medical Science, School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Institute of Biomedical Engineering, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China. Electronic address: gaoxiujun@tijmu.edu.cn.
authors.forename: Xiujun
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D007928:Lethal Dose 50; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D023382:Toxicity Tests, Acute
chemical_list: D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; D007785:Lactose
keywords: Lactosylated PLGA; Nanoparticle; Protein; Sustained release; ϵ-Polylysine