Journal article
Biodistribution, Metabolism, and in Vivo Gene Expression of Low Molecular Weight Glycopeptide Polyethylene Glycol Peptide DNA Co‐Condensates
Journal of pharmaceutical sciences, Vol.89(4), pp.499-512
04/2000
DOI: 10.1002/(SICI)1520-6017(200004)89:4<499::AID-JPS7>3.0.CO;2-V
PMID: 10737911
Abstract
The biodistribution, metabolism, cellular targeting, and gene expression of a nonviral peptide DNA gene delivery system was examined. 125I‐labeled plasmid DNA was condensed with low molecular weight peptide conjugates and dosed i.v. in mice to determine the influence of peptide DNA formulation parameters on specific gene targeting to hepatocytes. Optimal targeting to hepatocytes required the combined use of a triantennary glycopeptide (Tri‐CWK18) and a polyethylene glycol‐peptide (PEG‐CWK18) to mediate specific recognition by the asialoglycoprotein receptor and to reduce nonspecific uptake by Kupffer cells. Tri‐CWK18/PEG‐CWK18 DNA co‐condensates were stabilized and protected from metabolism by glutaraldehyde crosslinking. An optimized formulation targeted 60% of the dose to the liver with 80% of the liver targeted DNA localized to hepatocytes. Glutaraldehyde crosslinking of DNA condensates reduced the liver elimination rate from a t½ of 0.8 to 3.6 h. An optimized gene delivery formulation produced detectable levels of human α1‐antitrypsin in mouse serum which peaked at day 7 compared to no expression using control formulations. The results demonstrate the application of formulation optimization to improve the targeting selectivity and gene expression of a peptide DNA delivery system. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 499–512, 2000
Details
- Title: Subtitle
- Biodistribution, Metabolism, and in Vivo Gene Expression of Low Molecular Weight Glycopeptide Polyethylene Glycol Peptide DNA Co‐Condensates
- Creators
- Wendy T Collard - Divisions of Pharmaceutics and Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109‐1065Yongsheng Yang - Divisions of Pharmaceutics and Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109‐1065Kai Y Kwok - Divisions of Pharmaceutics and Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109‐1065Youmie Park - Divisions of Pharmaceutics and Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109‐1065Kevin G Rice - Divisions of Pharmaceutics and Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109‐1065
- Resource Type
- Journal article
- Publication Details
- Journal of pharmaceutical sciences, Vol.89(4), pp.499-512
- DOI
- 10.1002/(SICI)1520-6017(200004)89:4<499::AID-JPS7>3.0.CO;2-V
- PMID
- 10737911
- NLM abbreviation
- J Pharm Sci
- ISSN
- 0022-3549
- eISSN
- 1520-6017
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 04/2000
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984065318102771
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