title: Comparative investigations on in vitro serum stability of polymeric micelle formulations.
abstract: OBJECTIVE
  Stability of polymeric micelles upon injection is essential for a drug delivery system but is not fully understood. We optimized an analytical test allowing quantification of micellar stability in biofluids and applied it to a variety of block copolymer micelles with different hydrophobic block architechtures.
  
  
  METHODS
  Polymeric micelles were prepared from four different polymers and investigated via encapsulation of two fluorescent dyes. Samples were incubated in human serum; changes in Foerster Resonance Energy Transfer (FRET) were recorded as a function of time. This fluorescence-based approach was supported semi-quantitatively by results from Asymmetrical Flow Field-Flow-Fractionation (AF4).
  
  
  RESULTS
  After incubation experiments, micellar stability was determined by calculation of two stability-indicating parameters: residual micellar fractions (RMFs) and in vitro serum half-lives. Both parameters showed that PEG-PVPy micelles rapidly destabilized after 3 h (RMF < 45%), whereas PEG-PLA, PEG-PLGA and PEG-PCL micelles were far more stable (RMFs 65 to 98%).
  
  
  CONCLUSIONS
  This FRET-based assay is a valuable tool in evaluating and screening serum stability of polymeric micelles and revealed low serum stability of PEG-PVPy micelles compared to polyester-based micelles.
authors: Exploratory Pharmaceutical Development, Merck KGaA, Frankfurter Straße 250, 64293, Darmstadt, Germany.
authors: Tobias
authors: T
authors: Miller
authors: Reinhard
authors: R
authors: Rachel
authors: Ahmed
authors: A
authors: Besheer
authors: Senta
authors: S
authors: Uezguen
authors: Markus
authors: M
authors: Weigandt
authors: Achim
authors: A
authors: Goepferich
mesh_terms: D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008823:Micelles; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D044967:Serum / Q000378:metabolism*; D012995:Solubility
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers