Poly(2-oxazoline) block copolymer based formulations of taxanes: effect of copolymer and drug structure, concentration, and environmental factors†‡

Many current nanoformulations of taxanes are hampered by low drug-loading capacity and unfavorable physicochemical characteristics such a sl arge particles size (>100nm) and/or low size uniformity. We have previously reported on taxane nanoformulations, based on poly(2-oxazoline) polymeric micelles that display an extremely high taxane loading capacity (>40%w/w) and particle size below 50nm. Previous work was based on a triblock copolymer having poly(2-butyl-2oxazoline) as the hydrophobic block and poly(2-methyl-2-oxazoline) as the hydrophilic blocks. This paper explores the effects of various formulation parameters such as (i) the drug and polymer structure; (ii) the drug and polymer concentration; and (iii) the composition of aqueous medium on the solubilization behavior and physicochemical properties of the resulting formulations. In addition, in vitro anticancer activity is reported. Despite numerous variations of the hydrophobicity, polarity or additionofaromaticresiduesinthehydrophobiccore,thetriblockcopolymerwiththepoly(2-butyl-2-oxazoline)blockremains the polymer with the highest drug-loading capacity. Notably, the formulationwas easily scalablewith uncompromisedencapsulation efficacy, loading capacity, and physicochemical properties. The taxane formulations were stable upon storage (water, saline, and dextrose solution) for1–2weeks andcouldbelyophilizedandre-dispersedwithoutcompromisingthe formulation properties.Furthermore,the micelles remained stable upondilution. The drug-loaded poly(2-oxazoline) micelles showed high toxicityagainstseveralcancercell lines.Takentogether,theseresultsunderscorethepotentialof poly(2-oxazoline)micellesas formulation excipient for taxanes and possibly other hydrophobic drugs. Copyright © 2015 John Wiley & Sons, Ltd. Supporting information may be found in the online version of this paper.