Cationic surfactants in the form of nanoparticles and micelles elicit different human neutrophil responses: a toxicological study.
Cationic surfactants are an ingredient commonly incorporated into nanoparticles for clinical practicability; however, the toxicity of cationic surfactants in nanoparticles is not fully elucidated. We aimed to evaluate the inflammatory responses of cationic nanobubbles and micelles in human neutrophils. Soyaethyl morpholinium ethosulfate (SME) and hexadecyltrimethyl-ammonium bromide (CTAB) are the two cationic surfactants employed in this study. The zeta potential of CTAB nanobubbles was 80 mV, which was the highest among all formulations. Nanobubbles, without cationic surfactants, showed no cytotoxic effects on neutrophils in terms of inflammatory responses. Cationic nanobubbles caused a concentration-dependent cytotoxicity of degranulation (elastase release) and membrane damage (release of lactate dehydrogenase, LDH). Among all nanoparticles and micelles, CTAB-containing nanosystems showed the greatest inflammatory responses. A CTAB nanobubble diluent (1/150) increased the LDH release 80-fold. Propidium iodide staining and scanning electron microscopy (SEM) verified cell death and morphological change of neutrophils treated by CTAB nanobubbles. SME, in a micelle form, strengthened the inflammatory response more than SME-loaded nanobubbles. Membrane interaction and subsequent Ca(2+) influx were the mechanisms that triggered inflammation. The information obtained from this work is beneficial in designing nanoparticulate formulations for balancing clinical activity and toxicity.
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.
Tsong-Long
TL
Hwang
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA USA.
Calvin T
CT
Sung
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Ibrahim A
IA
Aljuffali
Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan.
Yuan-Ting
YT
Chang
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; Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan. Electronic address: fajy@mail.cgu.edu.tw.
Jia-You
JY
Fang
D000328:Adult; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000633:toxicity*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008823:Micelles; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D009336:Necrosis; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D010196:Pancreatic Elastase / Q000378:metabolism; D010316:Particle Size; D011419:Propidium / Q000378:metabolism; D013194:Staining and Labeling; D055672:Static Electricity; D013501:Surface-Active Agents / Q000633:toxicity*; D018675:Toxicity Tests; D055815:Young Adult
D002412:Cations; D008823:Micelles; D013501:Surface-Active Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D011419:Propidium; D004533:Egtazic Acid; D007770:L-Lactate Dehydrogenase; D010196:Pancreatic Elastase; D002118:Calcium
Cationic surfactants; Inflammation; Micelles; Nanobubbles; Neutrophils; Toxicity