Microneedles containing sodium carboxymethylcellulose (CMC) formulations were fabricated to include an external chitosan (CS) layer to modulate their hydration profile, an important parameter affecting their application as intradermal delivery devices and their storage. The microfabrication process was carried out under conditions that enabled the formation of polyelectrolyte complexes between these oppositely charged macromolecules. CMC-CS microneedles were characterized by water uptake in a humid environment, contact angle measurements, dissolution in aqueous solutions, and protein-release profiles. The results demonstrate that the microneedles containing CMC-CS formulations displayed suppressed moisture sensitivity in water vapors compared to their unmodified CMC counterparts while the maintaining quick protein-release characteristics required for their uses. This approach also showed the potential for sustained protein-release applications, as the CMC-CS formulations could be combined in layers to fabricate multicompartment microneedle coatings with delayed release characteristics. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 395-401, 2011