Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 203, Issue 1-2, Pages 81-88Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0378-5173(00)00435-X
Keywords
peptide DNA condensates; freeze-drying; lyoprotectant; polyethylene glycol; particle size; solubility; aggregation prevention
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Funding
- NIDCR NIH HHS [DE13004] Funding Source: Medline
- NIGMS NIH HHS [GM48049] Funding Source: Medline
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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 mu g/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 mu g/ml; however, higher DNA concentrations led to the formation of insoluble fibrous flocculates. Substitution of polyethylene glycol (PEG)-CWK18 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 mu g/ml. Alternatively, the steric layer created on the surface of PEG-CWK18 DNA condensates provides far more efficient lyoprotection, preserving their particle size at a concentration of 5 mg/ml without a bulking agent. (C) 2000 Elsevier Science B.V. All rights reserved.
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