title: Cationic additives in nanosystems activate cytotoxicity and inflammatory response of human neutrophils: lipid nanoparticles versus polymeric nanoparticles.
abstract: This report compares the effect of lipid and polymeric nanoparticles upon human neutrophils in the presence of cationic surfactants. Nanostructured lipid carriers and poly(lactic-co-glycolic) acid nanoparticles were manufactured as lipid and polymeric systems, respectively. Some cytotoxic and proinflammatory mediators such as lactate dehydrogenase (LDH), elastase, O2(•-), and intracellular Ca(2+) were examined. The nanoparticles showed a size of 170-225 nm. Incorporation of cetyltrimethylammonium bromide or soyaethyl morpholinium ethosulfate, the cationic surfactant, converted zeta potential from a negative to a positive charge. Nanoparticles without cationic surfactants revealed a negligible change on immune and inflammatory responses. Cationic surfactants in both nanoparticulate and free forms induced cell death and the release of mediators. Lipid nanoparticles generally demonstrated a greater response compared to polymeric nanoparticles. The neutrophil morphology observed by electron microscopy confirmed this trend. Cetyltrimethylammonium bromide as the coating material showed more significant activation of neutrophils than soyaethyl morpholinium ethosulfate. Confocal microscope imaging displayed a limited internalization of nanoparticles into neutrophils. It is proposed that cationic nanoparticles interact with the cell membrane, triggering membrane disruption and the following Ca(2+) influx. The elevation of intracellular Ca(2+) induces degranulation and oxidative stress. The consequence of these effects is cytotoxicity and cell death. Caution should be taken when selecting feasible nanoparticulate formulations and cationic additives for consideration of applicability and toxicity.
authors.affiliation: Cell Pharmacology Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan ; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan, Taiwan.
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Aljuffali
authors.affiliation: Department of Cosmetic Science, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan ; Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan.
authors.forename: Chwan-Fwu
authors.initials: CF
authors.lastname: Lin
authors.affiliation: Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan.
authors.forename: Yuan-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan ; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan ; Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan.
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Fang
mesh_terms: D002412:Cations; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000633:toxicity; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry / Q000633:toxicity
chemical_list: D002412:Cations; D002593:Cetrimonium Compounds; D008055:Lipids; D011108:Polymers; D000077286:Cetrimonium
keywords: cationic surfactant; inflammation; nanoparticle; neutrophil