Characterization of the Drug Retention and Pharmacokinetic Properties of Liposomal Nanoparticles Containing Dihydrosphingomyelin.
From: Department of Biochemistry and Molecular Biology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
Biochimica et biophysica acta
- Publish Date: May 2007
- ISSN: 0006-3002
- Volume: 1768
- Issue: 5
- Pages: 1121-7
- Medium: Print
- Language: English
- Citation (JAMA): Johnston Michael J W, Semple Sean C, Klimuk Sandy K, et al. Characterization of the Drug Retention and Pharmacokinetic Properties of Liposomal Nanoparticles Containing Dihydrosphingomyelin.. Biochim. Biophys. Acta May 2007;1768:1121-7
Abstract
The drug retention and circulation lifetime properties of liposomal nanoparticles (LN) containing dihydrosphingomyelin (DHSM) have been investigated. It is shown that replacement of egg sphingomyelin (ESM) by DHSM in sphingomyelin/cholesterol (Chol) (55/45; mol/mol) LN results in substantially improved drug retention properties both in vitro and in vivo. In the case of liposomal formulations of vincristine, for example, the half-times for drug release (T(1/2)) were approximately 3-fold longer for DHSM/Chol LN as compared to ESM/Chol LN, both in vitro and in vivo. Further increases in T(1/2) could be achieved by increasing the drug-to-lipid ratio of the liposomal vincristine formulations. In addition, DHSM/Chol LN also exhibit improved circulation lifetimes in vivo as compared to ESM/Chol LN. For example, the half-time for LN clearance (Tc(1/2)) at a low lipid dose (15 micromol lipid/kg, corresponding to 8 mg lipid/kg body weight) in mice was 3.8 h for ESM/Chol LN compared to 6 h for DHSM/Chol LN. In addition, it is also shown that DHSM/Chol LN exhibit much longer half-times for vincristine release as compared to LN with the “Stealth” lipid composition. It is anticipated that DHSM/Chol LN will prove useful as drug delivery vehicles due to their excellent drug retention and circulation lifetime properties.
Mesh Headings (Keywords): Animals, Cattle, Cholesterol, Drug Carriers, Female, Half-Life, Liposomes, Mice, Nanoparticles, Phase Transition, Sphingomyelins, Temperature, Vincristine
Check for Full Text / PubMed Unique Identifier (PMID): 17321495
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