title: A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells.
abstract: Dendrimers are hyperbranched macromolecules with well-defined topological structures and multivalent functionalization sites, but they may cause cytotoxicity due to the presence of cationic charge. Recently, we have introduced alkyne-terminated poly(amidoamine) (PAMAM) dendrons of different generations (G=2,3) into chitosan to obtain dendronized chitosan derivatives [Cs-g-PAMAM (G=2,3)], which exhibited a better water solubility and enhanced plasmid DNA transfection efficiency. In this study, we attempted to examine the impact of Cs-g-PAMAM (G=2,3) at different concentrations (25 μg/mL, 50 μg/mL, and 100 μg/mL) on the morphology, surface structure, and viability of rat red blood cells (RBCs). The results showed that treatment of RBCs with Cs-g-PAMAM (G=2,3) at 50 μg/mL and 100 μg/mL induced a slightly higher hemolysis than Cs, and Cs-g-PAMAM (G=3) caused a slightly higher hemolysis than Cs-g-PAMAM (G=2), but all values were <5.0%. Optical microscopic and atomic force microscopic examinations indicated that Cs-g-PAMAM (G=2,3) caused slight RBC aggregation and lysis. Treatment of RBCs with 100 μg/mL Cs-g-PAMAM (G=3) induced echinocytic transformation, and RBCs displayed characteristic irregular contour due to the folding of the periphery. Drephanocyte-like RBCs were observed when treated with 100 μg/mL Cs-g-PAMAM (G=3). Erythrocytes underwent similar shape transition upon treatment with Cs-g-PAMAM (G=2) or Cs. The roughness values (Rms) of RBCs incubated with Cs-g-PAMAM (G=2,3) were significantly larger than those for RBCs incubated with physiological saline (P<0.01), but the Rms showed no difference for Cs and Cs-g-PAMAM (G=2,3) (P>0.05). Furthermore, Cs-g-PAMAM (G=2,3) exhibited a lower cytotoxicity in human kidney 293T cells. These results indicate that Cs-g-PAMAM (G=2,3) are hemocompatible but may disturb membrane and lipid structures at higher concentrations. Further safety and biocompatibility evaluations are warranted for Cs-g-PAMAM. Our findings prove helpful for a better understanding of the advantages of combining PAMAM dendrimers and chitosan to design and develop new, safe, and effective drug delivery vehicles.
authors.affiliation: Guangdong Medical Universtity, Dongguan, Guangdong, People's Republic of China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Guangdong Medical Universtity, Dongguan, Guangdong, People's Republic of China.
authors.forename: Jiemei
authors.initials: J
authors.lastname: Li
authors.affiliation: Guangdong Medical Universtity, Dongguan, Guangdong, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Materials Science and Engineering, Drexel University, Philadelphia, PA, USA.
authors.forename: Junjie
authors.initials: J
authors.lastname: Deng
authors.affiliation: Guangdong Medical Universtity, Dongguan, Guangdong, People's Republic of China.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Guangdong Medical Universtity, Dongguan, Guangdong, People's Republic of China.
authors.forename: Peijie
authors.initials: P
authors.lastname: Fang
authors.affiliation: Guangdong Medical Universtity, Dongguan, Guangdong, People's Republic of China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000276:immunology*; D050091:Dendrimers / Q000737:chemistry; D004903:Erythrocyte Aggregation / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology*; D006461:Hemolysis / Q000187:drug effects; D006648:Histocompatibility; D066298:In Vitro Techniques; D007668:Kidney / Q000166:cytology / Q000276:immunology; D008055:Lipids / Q000737:chemistry; D018625:Microscopy, Atomic Force; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D050091:Dendrimers; D008055:Lipids; C104700:PAMAM Starburst; D048271:Chitosan
keywords: PAMAM; RBC; dendronized chitosan derivative; hemocompatibility; hemolysis