© 2021 Elsevier B.V.Electrospun nanofibers are promising drug delivery systems for transdermal applications with a release rate of the drug depending on the host polymer used. However, it is still a challenge to control (i.e., reduce) the release rate for hydrophilic drugs in order to provide long-term sustained release. In this study, we aimed to produce controlled release nanofibers to achieve long term drug release for transdermal applications. Pramipexole, which requires multiple doses per day, was selected as a hydrophilic model drug molecule and was electrospun with hydrophobic polycaprolactone polymer. To prevent burst release of the drug and provide a long-term release profile, nanofibers were coated with Parylene C or N using a chemical vapor deposition process. The effective thickness of nanofibers increased with the amount of Parylene coating. Parylene coating also enhanced the mechanical properties and hydrophobicity but decreased the bioadhesion values. Drug release and diffusion studies showed that Parylene coating successfully prevents drug burst release. Uncoated nanofibers completely released pramipexole within 12 h. A relatively low amount of Parylene N and C coating provided 81% and 52% drug release over 10 days, while increased Parylene N and C coating resulted in 27% and 12.6% drug release over a 30-day period, respectively. Parylene coating process offers the possibility of long-term controlled release kinetics including hydrophilic drugs.