Rapid clearance and proteolysis limit delivery and efficacy of protein therapeutics. Loading into biodegradable polymer nanocarriers (PNC) might protect proteins, extending therapeutic duration, but loading can be complicated by protein unfolding and inactivation. We encapsulated active enzymes into methoxy-poly(ethylene glycol- block-lactic acid) (mPEG-PLA) PNC with a freeze-thaw double emulsion ( J. Controlled Release 2005, 102 (2), 427-439). On the basis of concepts of amphiphile self-assembly, we hypothesized that the copolymer block ratio that controls spontaneous curvature would influence PNC morphology and loading. We examined PNC yield, shape, stability, loading, activity, and protease resistance of the antioxidant enzyme, catalase. PNC transitioned from spherical to filamentous shapes with increasing hydrophobic polymer fraction, consistent with trends for self-assembly of lower MW amphiphiles. Importantly, one diblock copolymer formed filamentous particles loaded with significant levels of protease-resistant enzyme, demonstrating for the first time encapsulation of an active therapeutic enzyme into filamentous carriers. PNC morphology also greatly influenced its degradation, offering a new means of controlled delivery.