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Journal article
A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells
Drug design, development and therapy, v 9(default), pp 2635-2645
01 Jan 2015
PMID: 25999697
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 mu g/mL, 50 mu g/mL, and 100 mu g/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 mu g/mL and 100 mu g/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 mu g/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 mu g/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.
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Details
- Title
- A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells
- Creators
- Yanfang Zhou - Guangdong Medical CollegeJiemei Li - Guangdong Med Univ, Dongguan 523808, Guangdong, Peoples R ChinaFang Lu - Guangdong Medical CollegeJunjie Deng - Drexel UniversityJiahua Zhang - Guangdong Medical CollegePeijie Fang - Guangdong Medical CollegeXinsheng Peng - Guangdong Medical CollegeShu-Feng Zhou - University of South FloridaJingjing Li - Urban Health Collaborative (2015-)
- Publication Details
- Drug design, development and therapy, v 9(default), pp 2635-2645
- Publisher
- Dove Medical Press Ltd
- Number of pages
- 11
- Grant note
- 201308440229; 201408440141 / China Scholarship Council
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Urban Health Collaborative
- Web of Science ID
- WOS:000354467600002
- Scopus ID
- 2-s2.0-84929579767
- Other Identifier
- 991019173424304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Chemistry, Medicinal
- Pharmacology & Pharmacy