Degradable dextran microspheres for the controlled release of liposomes.
A novel delivery concept based on the encapsulation of liposomes in biodegradable dextran microspheres was developed. The microspheres were prepared using a two-phase system, consisting of water/poly(ethylene glycol), and water/methacrylated dextran. Liposomes were encapsulated almost quantitatively and in their intact form, and were released with full preservation of their integrity. The effects of microsphere water content, degree of methacrylate substitution, and type of dextran derivative used on the release rate were investigated. The release of the liposomes from the dextran microspheres was fully controlled by the degradation rate of the spheres. This resulted, after a lag time, in a pulsed release of the liposomes from relatively rapidly degrading microspheres. On the other hand, slower degrading microspheres resulted in sustained release of liposomes over 100 days. The degradation rate of the dextran microspheres, in turn, depended on the water content, the degree of methacrylate substitution, and type of hydrolytically sensitive spacer present in the cross-links.
Stenekes
R J
RJ
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), University of Utrecht, PO Box 80082, 3508 TB Utrecht, The Netherlands.
Loebis
A E
AE
Fernandes
C M
CM
Crommelin
D J
DJ
Hennink
W E
WE
D003911:Dextrans / Q000008:administration & dosage*; D004337:Drug Carriers; D008081:Liposomes / Q000008:administration & dosage*; D008863:Microspheres
D003911:Dextrans; D004337:Drug Carriers; D008081:Liposomes