Drug Loading of Polymeric Micelles

To gain mechanistic insights into drug loading and lyophilization of polymeric micelles. 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. 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 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. 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.