Journal article
Strategies for maintaining the particle size of peptide DNA condensates following freeze-drying
International journal of pharmaceutics, Vol.203(1), pp.81-88
2000
DOI: 10.1016/S0378-5173(00)00435-X
PMID: 10967430
Abstract
The particle size of peptide DNA condensates were studied after freeze-drying and rehydration as a function of sugar excipient, concentration, pH, DNA concentration, and peptide condensing agent. In the absence of an excipient, freeze-dried 50 μg/ml AlkCWK
18 (iodoacetic acid alkylated Cys-Typ-Lys
18) DNA condensates formed large fibrous flocculates on rehydration. Of the sugars tested as lyoprotectants, sucrose proved most effective at preserving particle size during rehydration. The addition of 5 wt/vol% sucrose preserved a mean particle diameter of less than 50 nm during rehydration of AlkCWK
18 DNA condensates prepared at DNA concentrations up to 200 μg/ml; however, higher DNA concentrations led to the formation of insoluble fibrous flocculates. Substitution of polyethylene glycol (PEG)-CWK
18 as a DNA condensing peptide eliminated the need for sucrose, resulting in peptide DNA condensates that retained particle size when rehydrated in water or normal saline at concentrations up to 5 mg/ml. The results suggest that sucrose functions primarily as a bulking agent during freeze-drying that only preserves the particle size of AlkCWK
18 DNA condensates up to a maximum concentration of 200 μg/ml. Alternatively, the steric layer created on the surface of PEG-CWK
18 DNA condensates provides far more efficient lyoprotection, preserving their particle size at a concentration of 5 mg/ml without a bulking agent.
Details
- Title: Subtitle
- Strategies for maintaining the particle size of peptide DNA condensates following freeze-drying
- Creators
- Kai Y Kwok - Divisions of Pharmaceutics, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USARoger C Adami - Divisions of Pharmaceutics, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USAKelly C Hester - Divisions of Pharmaceutics, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USAYoumie Park - Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USASteve Thomas - Divisions of Pharmaceutics, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USAKevin G Rice - Divisions of Pharmaceutics, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USA
- Resource Type
- Journal article
- Publication Details
- International journal of pharmaceutics, Vol.203(1), pp.81-88
- DOI
- 10.1016/S0378-5173(00)00435-X
- PMID
- 10967430
- NLM abbreviation
- Int J Pharm
- ISSN
- 0378-5173
- eISSN
- 1873-3476
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 2000
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984065699202771
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