Controlled drug delivery involves multidisciplinary scientific approach. Therapeutic proteins, peptides and genes need to be protected from degradation after delivering them in a biological environment. One common and convenient way to deliver these biomolecules is by incorporating them in a suitable biodegradable, biocompatible, and a non-toxic polymeric biomaterial, which can be implanted at the site of drug delivery and then released at the predetermined rate. Many factors affect the release rate. The present study addresses the particle size distribution of the dispersed, protein phase. Compositional quenching was used to produce sub-micron scale dispersions. This technique works on the principle of flash devolatilization, which rapidly quenches a homogeneous polymer-polymer-solvent system from the single phase region to the two phases by spinodal decomposition. Chitosan, a waste product from the seafood industry, was used as a polymer matrix. It is a natural, swellable, biodegradable, biocompatible, and polycationic polymer soluble in (1% v/v) aqueous acetic acid. Green fluorescent protein (GFP) was used as the model protein, it is stable in the pH range of 5.5 - 12 and temperatures up to 70 ^oC, and is a very useful tool in bioprocess monitoring, gene expression and in vivo protein interaction studies. Compositional quenching was used to incorporate GFP in chitosan with a quality of sub-micron particle size. Fluorescent microscopy and ImageJ analysis were used to study the particle size distribution of GFP in the matrix. Swelling of the chitosan was controlled by ionically cross-linking it with an anionic sodium tripolyphosphate solution. The release rates of GFP from cross-linked and non cross-linked chitosan-GFP films in PBS solution at 37 ^oC were monitored by using fluorometry.