The aim of this study is to develop electrospun gelatin nanofibers based drug delivery carrier to achieve controlled and sustainable release of hydrophobic drug (piperine) for prolonged time. To accomplish this, we devised some strategies such as sandwiching the drug loaded gelatin nanofiber mesh with another gelatin nanofiber matrix without drug (acting as diffusion barrier), sequential crosslinking and finally, a combination of both. As fabricated multilayered electrospun nanofibers mesh was first characterized in terms of degradation study, morphology, drug-polymer interactions, thermal stability followed by studying their release kinetics in different physiological pH as per the gastrointestinal tract. Our results show that with optimized diffusional barrier support and sequential crosslinking together, a zero order sustained drug release up to 48 h may be achieved with a flexibility to vary the drug loading as per the therapeutic requirements. This work lays out the possibility of systematic design of multilayer nano-fiber mesh of a biopolymer as a drug delivery vehicle for hydrophobic drugs with a desired signature of zero order release for prolonged duration. © 2017 Elsevier B.V.