Avoiding Hemolytic Anemia by Understanding the Effect of the Molecular Architecture of Gemini Surfactants on Hemolysis

Abstract

Hemolytic behavior of a series of different categories of Gemini surfactants was determined in their low concentration range. Cationic Gemini surfactants of different molecular architectures prove to be highly cytotoxic even at 0.1 mM. Anionic and amino acid-based Gemini surfactants were minimally cytotoxic, although their toxicity was concentration-dependent. With respect to monomeric surfactants of comparable hydrocarbon chain lengths, cationic Gemini surfactants were much more toxic than anionic Gemini surfactants. Incubation temperature was another important parameter that significantly drove the hemolysis irrespective of the molecular structure of the surfactant. Results indicated that the surface activity or liquid−blood cell membrane adsorption tendency of a surfactant molecule determined the degree of hemolytic anemia. Greater surface activity induced greater cytotoxicity, especially when the surfactant possessed a stronger ability to interact with the membrane proteins through hydrophilic interactions. That provided cationic Gemini surfactants a higher ability for hemolytic anemia because they were able to interact with an electronegative cell membrane with favorable interactions in comparison to anionic or amino acid-based Gemini surfactants. These findings are expected to help in designing surface-active drugs with a suitable molecular architecture that can avoid hemolytic anemia.

Hemolytic Response of Iron Oxide Magnetic Nanoparticles at the Interface and in Bulk: Extraction of Blood Cells by Magnetic Nanoparticles

“…The Gemini surfactant-stabilized NPs show significantly high % hemolysis (≥70%) in comparison to monomeric stabilized NPs, which is quite expected because of the stronger amphiphilicity contributed by Gemini surfactants [hydrophilic–lipophilic balance (HLB) values, Table S1]. Because of that both D10HD and D12HD-stabilized magnetic NPs also possess greater blood cell extraction ability (≤10%) in comparison to monomeric stabilized NPs (≤5%). As shown in Figure b, we compare the results of monomeric cationic surfactant-stabilized NPs (Figures S65 and S70–S73) with single (DTAB and TTAB) and double (12–0–12, 14–0–14, 16–0–16, i.e., n –0– n ) hydrocarbon chains where “0” stands for no spacer group in the head group region.…”

“…A comparison between the results of Figures and indicates that surface-active magnetic NPs can induce significant hemolytic effects when placed at the aqueous–air interface without incorporating into the aqueous bulk especially when they are stabilized with Gemini surfactants. Both anionic (Figure a) and cationic (Figure c,d) Gemini surfactants possess strong potential to break the blood cell membrane while being adsorbed on magnetic NPs, which increases with the length of the hydrocarbon chain and methylene groups in the spacer. It demonstrates that NPs when placed at the interface still possess significant capability to interact and break the blood cell membrane through different functional groups of adsorbed amphiphilic molecules on the NP surface.…”

“…Surfactants with an HLB value in the range of ∼5–15 possess strong cell membrane disrupting ability because they can interact with lipid head groups as well as bilayer simultaneously. Both anionic SDS and cationic CTAB found to disrupt the blood cell membrane because lipid bilayer is lined with zwitterionic head groups of phospholipid molecules . The stronger the amphiphilicity of a surface-adsorbed surfactant (e.g., n –0– n and n –2– n of Figure ), greater is the membrane disruption ability, which may result in the extracellular vesicles (Figure a) or more significantly holes (Figure b) formation.…”

“…Hemolytic assay was performed on human red blood cells from a healthy human donor . All experiments were performed with fresh blood from two to three selected donors within few hours.…”

Colloidal Stabilization of Sodium Dilauraminocystine for Selective Nanoparticle–Nanoparticle Interactions: Their Screening and Extraction by Iron Oxide Magnetic Nanoparticles

“…Chloroauric acid (HAuCl 4 ), silver nitrate (AgNO 3 ), sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), dodecyldimethyl-3-ammonio-1-propanesulfonate (DPS), didodecyldimethylammonium bromide (12-0-12), ferric chloride (FeCl 3 ), and ferrous sulfate (Fe 2 SO 4 ), all more than 99% pure, were obtained from Aldrich; dimethylene- (16-2-16), trimethylene- (16-3-16), tetramethylene- (16-4-16), pentamethylene- (16-5-16), hexamethylene bis­(hexadecyldimethylammonium bromide) (16-6-16), dimethylene- (12-2-12), hexamethylene bis­(dodecyldimethylammonium bromide) (12-6-12), tris (2-(dodecyldimethylammonio) ethyl)­amine tribromide (TriCAT), and SDLC were synthesized as reported previously. , Double distilled water was used for all preparations. The molecular structures of surfactants used in this study are presented in Figure S1 in the Supporting Information.…”