Protein drug delivery is challenging the conventional dosage forms such as tablets; gelatin capsules, and intramuscular and subcutaneous injections. Many new approaches to deliver protein drugs have been tried. These approaches are using either hydrophobic polymers or hydrophilic polymers. Since both the hydrophobic and the hydrophilic polymers have their own intrinsic problems, little or no progress has been made in protein drug delivery. in this study, a hydrophobic polymer and a hydrophilic polymer are combined by using a novel method to promote their advantages and overcome their problems. This combination will be conducted in a nontraditional way to create a novel protein drug delivery system. The traditional combination of hydrophobic polymers and hydrophilic polyniers uses either physical mixing/blending of the two types of polymers or chemical copolymerization of a hydrophobic monomer with a hydrophilic monorner. Both of these two traditional approaches give a homogeneously structured matrix. A kind of heterogeneous (or domain) structure is to be produced through the nontraditional combination of a hydrophobic polymer and a hydrophilic polymer in this proposal. Namely, two polymers will be combined in a manner that the hydrophobic polymer will be formulated as microspheres and the hydrophilic polymer will be formulated as hydrogel nanoparticles. Then, the hydrogel nanoparticles will be combined with the hydrophobic polymeric microspheres. The protein drugs will first be encapsulated in the hydrogel nanoparticles. Then, the protein-containing hydrogel nanoparticles will be further loaded in the hydrophobic polymer microspheres. The hydrogel provides a non- denaturing microenvironment for protein drugs while the hydrophobic polymer provides an inert carrier for prolonged release of protein drugs. Therefore, proposed is a new protein drug delivery system having advantage of (1) prolonged protein release and (2) prevention of protein drugs from biological activity loss. The hydrophobic polymer to be used is biodegradable poly(lactic-co-glycolic acid). The hydrophilic polymer to be tried will be chosen from natural or synthetic biodegradable polymers including gelatin, starch, and polyesteramides. The final dosage form of this composite is injectable microparticles. Therefore, this novel delivery system has the characteristics of ease of administration to patient as well as biodegradability.