title: A small variation in average particle size of PLGA nanoparticles prepared by nanoprecipitation leads to considerable change in nanoparticles' characteristics and efficacy of intracellular delivery.
abstract: In this study, it was aimed to investigate characteristics and intracellular delivery of two different-sized PLGA nanoparticles in ouzo region by considering number of nanoparticles. To determine the effect of formulation parameters on average particle size, Dil labeled nanoparticles were prepared using a three-factor, two-level full factorial statistical experimental design. PLGA230(230.8 ± 4.32 nm) and PLGA160(157.9 ± 6.16 nm) nanoparticles were obtained by altering polymer amount based on experimental design results and characterized. Same number of PLGA230and PLGA160nanoparticles per cell were applied onto HEK293 cells; then, cytotoxicity, uptake kinetics and mechanism were evaluated by flow cytometry and fluorescent microscopy. Also same weight of PLGA230and PLGA160nanoparticles were applied and cellular uptake of these nanoparticles was evaluated. It was found that PLGA230nanoparticles had higher encapsulation efficiency and slower dye release compared to PLGA160nanoparticles. When they were applied at same counts per cell, PLGA230nanoparticles displayed faster and higher intracellular dye transfer than PLGA160nanoparticles. On the other hand, PLGA160appeared to be a more effective vehicle than PLGA230when applied at the same weight concentration. It was also shown that for both nanoparticles, HEK293 cells employed macropinocytic, caveolae- and clathrin-mediated endocytic pathways.
authors.affiliation: a Department of Pharmaceutical Technology, Faculty of Pharmacy , Hacettepe University , Ankara , Turkey.|b Department of Pharmaceutical Technology, Faculty of Pharmacy , Erciyes University , Kayseri , Turkey.
authors.forename: Adem
authors.initials: A
authors.lastname: Sahin
authors.affiliation: c Department of Basic Oncology , Hacettepe University Cancer Institute , Ankara , Turkey.
authors.forename: Gunes
authors.initials: G
authors.lastname: Esendagli
authors.affiliation: d Elixir Pharmaceutical Research and Development Corporation , Ankara , Turkey.
authors.forename: Firat
authors.initials: F
authors.lastname: Yerlikaya
authors.affiliation: a Department of Pharmaceutical Technology, Faculty of Pharmacy , Hacettepe University , Ankara , Turkey.
authors.forename: Secil
authors.initials: S
authors.lastname: Caban-Toktas
authors.affiliation: c Department of Basic Oncology , Hacettepe University Cancer Institute , Ankara , Turkey.
authors.forename: Digdem
authors.initials: D
authors.lastname: Yoyen-Ermis
authors.affiliation: c Department of Basic Oncology , Hacettepe University Cancer Institute , Ankara , Turkey.
authors.forename: Utku
authors.initials: U
authors.lastname: Horzum
authors.affiliation: b Department of Pharmaceutical Technology, Faculty of Pharmacy , Erciyes University , Kayseri , Turkey.
authors.forename: Yesim
authors.initials: Y
authors.lastname: Aktas
authors.affiliation: e Irma Lerma Rangel College of Pharmacy, Texas A&M University , TX , USA.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Khan
authors.affiliation: f Institut Galien Paris-Sud UMR CNRS 8612, Faculty of Pharmacy , University Paris-Sud XI , Châtenay-Malabry , France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.affiliation: a Department of Pharmaceutical Technology, Faculty of Pharmacy , Hacettepe University , Ankara , Turkey.
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Capan
mesh_terms: D001692:Biological Transport; D011232:Chemical Precipitation; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D019344:Lactic Acid / Q000737:chemistry* / Q000378:metabolism*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Nanoparticles; cellular uptake mechanism; intracellular delivery; nanoprecipitation; particle size; poly(lactic-co-glycolic acid)