A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells
Yanfang Zhou,1,* Jiemei Li,1,* Fang Lu,1 Junjie Deng,2 Jiahua Zhang,1 Peijie Fang,1 Xinsheng Peng,1 Shu-Feng Zhou3 1Guangdong Medical Universtity, Dongguan, Guangdong, People’s Republic of China; 2Department of Materials Science and Engineering, Drexel University, Philadelphia, PA, USA; 3...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2015-05-01
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| Series: | Drug Design, Development and Therapy |
| Online Access: | http://www.dovepress.com/a-study-on-the-hemocompatibility-of-dendronized-chitosan-derivatives-i-peer-reviewed-article-DDDT |
| _version_ | 1819204993915289600 |
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| author | Zhou YF Li JM Lu F Deng JJ Zhang JH Fang PJ Peng XS Zhou SF |
| author_facet | Zhou YF Li JM Lu F Deng JJ Zhang JH Fang PJ Peng XS Zhou SF |
| author_sort | Zhou YF |
| collection | DOAJ |
| description | Yanfang Zhou,1,* Jiemei Li,1,* Fang Lu,1 Junjie Deng,2 Jiahua Zhang,1 Peijie Fang,1 Xinsheng Peng,1 Shu-Feng Zhou3 1Guangdong Medical Universtity, Dongguan, Guangdong, People’s Republic of China; 2Department of Materials Science and Engineering, Drexel University, Philadelphia, PA, USA; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA *These authors contributed equally to this work 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. Keywords: dendronized chitosan derivative, PAMAM, RBC, hemolysis, hemocompatibility |
| first_indexed | 2024-12-23T04:44:38Z |
| format | Article |
| id | doaj.art-3ca9f41eb9ca40e288ff4b25e20632c2 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-23T04:44:38Z |
| publishDate | 2015-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-3ca9f41eb9ca40e288ff4b25e20632c22022-12-21T17:59:41ZengDove Medical PressDrug Design, Development and Therapy1177-88812015-05-012015default2635264521730A study on the hemocompatibility of dendronized chitosan derivatives in red blood cellsZhou YFLi JMLu FDeng JJZhang JHFang PJPeng XSZhou SFYanfang Zhou,1,* Jiemei Li,1,* Fang Lu,1 Junjie Deng,2 Jiahua Zhang,1 Peijie Fang,1 Xinsheng Peng,1 Shu-Feng Zhou3 1Guangdong Medical Universtity, Dongguan, Guangdong, People’s Republic of China; 2Department of Materials Science and Engineering, Drexel University, Philadelphia, PA, USA; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA *These authors contributed equally to this work 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. Keywords: dendronized chitosan derivative, PAMAM, RBC, hemolysis, hemocompatibilityhttp://www.dovepress.com/a-study-on-the-hemocompatibility-of-dendronized-chitosan-derivatives-i-peer-reviewed-article-DDDT |
| spellingShingle | Zhou YF Li JM Lu F Deng JJ Zhang JH Fang PJ Peng XS Zhou SF A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells Drug Design, Development and Therapy |
| title | A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells |
| title_full | A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells |
| title_fullStr | A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells |
| title_full_unstemmed | A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells |
| title_short | A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells |
| title_sort | study on the hemocompatibility of dendronized chitosan derivatives in red blood cells |
| url | http://www.dovepress.com/a-study-on-the-hemocompatibility-of-dendronized-chitosan-derivatives-i-peer-reviewed-article-DDDT |
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