title: Drug loading of polymeric micelles.
abstract: OBJECTIVE
  To gain mechanistic insights into drug loading and lyophilization of polymeric micelles.
  
  
  METHODS
  PEGylated poly-4-(vinylpyridine) micelles were loaded with dexamethasone. Three different methods were applied and compared: O/W emulsion, direct dialysis, cosolvent evaporation. Micellar dispersions with the highest drug load were lyophilized with varying lyoprotectors: sucrose, trehalose, maltose, a polyvinylpyrrolidine derivative, and β-cyclodextrin derivatives. For comparison, other PEGylated block copolymer micelles (PEGylated polylactic acid, polylactic acid-co-glycolic acid, polycaprolactone) were freeze-dried.
  
  
  RESULTS
  Drug loading via direct dialysis from acetone was a less effective loading method which led to dexamethasone loads <2% w/w. O/W emulsion technique from dichlormethane increased drug load up to ~13% w/w; optimized cosolvent evaporation increased load up to ~19% w/w. An important step for cosolvent evaporation was solubility screen of the drug prior to preparation. Loading was maintained upon lyophilization with β-cyclodextrins which proved to be versatile stabilizers for other block copolymer micelles.
  
  
  CONCLUSIONS
  Careful solvent selection prior to cosolvent evaporation was a beneficial approach to load hydrophobic drugs into polymeric micelles. Moreover, β-cyclodextrins could be used as versatile lyoprotectors for these micelles.
authors.affiliation: Merck KGaA, Exploratory Pharmaceutical Development, Frankfurter Straße 250, 64293, Darmstadt, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Miller
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: van Colen
authors.forename: Bjoern
authors.initials: B
authors.lastname: Sander
authors.forename: Mariola Monika
authors.initials: MM
authors.lastname: Golas
authors.forename: Senta
authors.initials: S
authors.lastname: Uezguen
authors.forename: Markus
authors.initials: M
authors.lastname: Weigandt
authors.forename: Achim
authors.initials: A
authors.lastname: Goepferich
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying / Q000379:methods*; D019344:Lactic Acid / Q000737:chemistry; D008823:Micelles; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D005079:Excipients; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D011145:Polyvinyls; D047392:beta-Cyclodextrins; C019535:poly(4-vinylpyridine); D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D003907:Dexamethasone