Hydrogel particles have an historic presence in the field of drug formulation and delivery. Applications of particulate forms of gel materials continue to expand as a result of enhanced control over physicochemical properties including particle size, degradability, and environmental responsiveness. Here, acid-labile poly(N-vinylformamide) (PNVF) nanogels similar to 100 nm in diameter were synthesized via inverse emulsion polymerization of N-vinylformamide in the presence of a ketal-containing cross-linker. The dissolution half-life of nanogels proved to be dramatically faster at low pH. Nanogels with a monomer: cross-linker ratio of seven demonstrated a 90 min half-life at pH 5.8 compared to similar to 57 It at pH 7.4. Approximately 95% of lysozyme encapsulated in nanogels released over 200 min at pH 5.8 compared to only similar to 15% released at pH 7.4. The encapsulation efficiency was moderate with optimal conditions leading to similar to 60% encapsulation efficiency. In addition, released lysozyme retained about 50% of the original activity. Large differentials in PNVF nanogel dissolution time and protein release in response to slight changes in pH may ultimately provide a mechanism to selectively deliver macromolecular therapeutics to acidic tissues or intracellular vesicles.