title: Controlled release of liposomes from biodegradable dextran microspheres: a novel delivery concept.
abstract: OBJECTIVE
  To design liposome-loaded microspheres, which release the liposomes in a time-controlled manner and in intact form.
  
  
  METHODS
  Liposomes were encapsulated in biodegradable dextran-based microspheres, which were prepared using an aqueous two phase system consisting of poly(ethylene glycol) and methacrylated dextran. The effects of liposome size and membrane fluidity, microsphere water content, degree of methacrylate substitution, and type of dextran derivative used, on encapsulation efficiency, release, and integrity of the liposomes were investigated.
  
  
  RESULTS
  Liposomes were entrapped in dextran-based microspheres quantitatively and with full preservation of their integrity. Liposomes with a low, as well as with a high membrane fluidity, were released from the microspheres in their intact form and with preservation of their size. Release kinetics depended only on the degradation rate of the microspheres. For rapidly degrading systems, pulsed release was observed and the time after which the pulse occurred (from 5 until 25 days) could be tailored by the gel characteristics such as initial water content, degree of methacrylate substitution, and type of hydrolytically sensitive spacer present in the cross-links. This delay time was not dependent on the size of the liposomes in the range studied (0.1-0.2 microm). Microspheres which degraded more slowly showed, after a certain delay time, sustained release of the liposomes extended up to 100 days.
  
  
  CONCLUSIONS
  A novel drug delivery concept based on the encapsulation of liposomes in biodegradable dextran-based microspheres was designed. The system released the liposomes in intact form in a controlled way after a prolonged period of time.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, The Netherlands. R.J.H.Stenekes@pharm.uu.nl
authors.forename: R J
authors.initials: RJ
authors.lastname: Stenekes
authors.forename: A E
authors.initials: AE
authors.lastname: Loebis
authors.forename: C M
authors.initials: CM
authors.lastname: Fernandes
authors.forename: D J
authors.initials: DJ
authors.lastname: Crommelin
authors.forename: W E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008560:Membrane Fluidity; D008856:Microscopy, Fluorescence; D008863:Microspheres
chemical_list: D004337:Drug Carriers; D008081:Liposomes