Abstract: The polymeric blend of sericin and alginate has already shown good results for the incorporation of naproxen, achieving delayed and prolonged release. Thus, in this paper, it was aimed to optimize formulations of naproxen-loaded sericin and alginate blend, using the technique of experimental design. Initial amounts of alginate and drug were evaluated on entrapment efficiency, drug loading and time to release 85% of drug (t85). Efficiency was not affected statistically, while drug loading was higher for higher amounts of naproxen. In addition, the longest release times were achieved for greater amounts of drug and/or alginate, and the presence of sericin proved to be essential to extend the release of naproxen. The analytical characterizations of the particles showed the incorporation of the drug mainly in its original crystalline form, with part being physically mixed with the matrix. In addition, both the matrix and the drug loaded matrix demonstrated biocompatibility with HaCaT cell line Ver menos