| Enhancing polysaccharide-mediated delivery of nucleic acids through functionalization with secondary and tertiary amines. | |
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MedLine Citation:
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PMID: 18393895 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chitosan is a polysaccharide that has generated significant interest as a non-viral gene delivery vehicle due to its cationic and biocompatible characteristics. However, transfection efficiency of chitosan is significantly lower compared to other cationic gene delivery agents, e.g. polyethyleneimine (PEI), dendrimers or cationic lipids. This is primarily attributed to its minimal solubility and low buffering capacity at physiological pH leading to poor endosomal escape of the gene carrier and inefficient cytoplasmic decoupling of the complexed nucleic acid. Here we have developed an imidazole acetic acid (IAA)-modified chitosan to introduce secondary and tertiary amines to the polymer in order to improve its endosomal buffering and solubility. The modified polymer was characterized by ninhydrin and (1)H NMR assays for degree of modification, while buffering and solubility were analyzed by acid titration. Nanocomplex formation, studied at various polymer-nucleic acid ratios, showed an increase in particle zeta potential for chitosan-IAA, as well as an increase in the effective diameter. Up to 100-fold increase in transfection efficiency of pDNA was seen for chitosan-IAA as compared to native chitosan, nearly matching that of PEI. In addition, transfection of siRNA by the modified polymers showed efficient gene knockdown equivalent to commercially available siPORT Amines. Collectively, these results demonstrate the potential of the imidazole-grafted chitosan as a biocompatible and effective delivery vehicle for both pDNA and siRNA. |
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Authors:
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Bilal Ghosn; Sudhir Pai Kasturi; Krishnendu Roy |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Current topics in medicinal chemistry Volume: 8 ISSN: 1873-4294 ISO Abbreviation: Curr Top Med Chem Publication Date: 2008 |
Date Detail:
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Created Date: 2008-04-08 Completed Date: 2008-05-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101119673 Medline TA: Curr Top Med Chem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 331-40 Citation Subset: IM |
Affiliation:
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Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amines
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adverse effects,
chemistry* Cell Line Cell Survival / drug effects Chitosan / adverse effects, chemistry* Gene Transfer Techniques* Humans Molecular Structure Nanoparticles / chemistry* Nucleic Acids / administration & dosage* |
| Chemical | |
Reg. No./Substance:
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0/Amines; 0/Nucleic Acids; 9012-76-4/Chitosan |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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