1. Characterization of the drug retention and pharmacokinetic properties of liposomal nanoparticles containing dihydrosphingomyelin
- Author
-
Johnston, Michael J.W., Semple, Sean C., Klimuk, Sandy K., Ansell, Steve, Maurer, Norbert, and Cullis, Pieter R.
- Subjects
- *
PHARMACOKINETICS , *NANOPARTICLES , *VINCRISTINE , *DRUG delivery systems - Abstract
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 (Tc1/2) at a low lipid dose (15 μmol 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. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF