Drug Loading of Polymeric Micelles

作者：Miller Tobias; van Colen Gwenaelle; Sander Bjoern; Golas Mariola Monika; Uezguen Senta; Weigandt Markus; Goepferich Achim^*

来源：Pharmaceutical Research, 2013, 30(2): 584-595.

DOI：10.1007/s11095-012-0903-5

• cosolvent evaporation
• dexamethasone
• direct dialysis
• drug load
• freeze-drying
• HP beta CD
• lyophilization
• O/W emulsion
• polymeric micelles
• polypseudorotaxane
• SBE beta CD
• beta-cyclodextrins

To gain mechanistic insights into drug loading and lyophilization of polymeric micelles. %26lt;br%26gt;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 beta-cyclodextrin derivatives. For comparison, other PEGylated block copolymer micelles (PEGylated polylactic acid, polylactic acid-co-glycolic acid, polycaprolactone) were freeze-dried. %26lt;br%26gt;Drug loading via direct dialysis from acetone was a less effective loading method which led to dexamethasone loads %26lt; 2% w/w. O/W emulsion technique from dichlormethane increased drug load up to similar to 13% w/w; optimized cosolvent evaporation increased load up to similar 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 beta-cyclodextrins which proved to be versatile stabilizers for other block copolymer micelles. %26lt;br%26gt;Careful solvent selection prior to cosolvent evaporation was a beneficial approach to load hydrophobic drugs into polymeric micelles. Moreover, beta-cyclodextrins could be used as versatile lyoprotectors for these micelles.

• 出版日期2013-2