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Fenofibrate is a lipophilic drugused in hypercholesterolemia andhypertriglyceridemia as a lipid-regulating agent; however, it is characterizedby poor water solubility and low dissolution rate, which result ina low oral bioavailability. In the present study, sericin/poly(ethylcyanoacrylate)nanospheres are synthesized by interfacial polymerization in aqueousmedia and investigated as a novel sericin-based delivery system forimproved and enhanced oral bioefficacy of fenofibrate. The incorporationof sericin into the prepared cyanoacrylate nanoparticles and theirspherical shape are confirmed by Lowry assay and scanning electronmicroscopy, respectively. Hydrophilic and mucoadhesive propertiesof the synthesized nanospheres are also evaluated. Finally, both invitro release and in vivo studies are performed and the oral absorbableamount of fenofibrate is calculated to be higher than 70% when incorporatedinto the polymeric material, reducing the levels of total cholesterol(TC), triacylglycerols (TG), very low-density lipoproteins (VLDL),and low-density lipoproteins (LDL) compared to fenofibrate alone. [ABSTRACT FROM AUTHOR]