Dual temperature and pH responsive nanofiber formulations prepared by electrospinning

We report a dual-responsive drug delivery system prepared by electrospinning. Blend fibers of poly(N-vinylcaprolactam) (PNVCL) and ethyl cellulose (EC) were first prepared, with the aim of developing thermoresponsive sustained release formulations. Eudragit L100-based fibers were then generated to yield pH-sensitive materials. Attempts to produce three-polymer fibers of EC, PNVCL and Eudragit were unsuccessful, and therefore hybrid mats containing two fiber populations (one made of PNVCL/EC, one comprising Eudragit) were instead fabricated by twin-jet electrospinning. Analogous drug-loaded versions of all the formulations were also prepared containing ketoprofen (KET). The fibers were largely smooth and homogeneous, and the addition of KET did not affect their morphology. The PNVCL-containing fiber mats changed from being hydrophilic to hydrophobic when the temperature was increased through the lower critical solution temperature of 33 °C. In vitro drug release profiles showed that the hybrid fiber mats were able to combine the properties of the three polymers, exhibiting both pH-sensitive and thermosensitive properties with sustained release. In addition, they were found to be nontoxic and suitable for cell growth. This study therefore demonstrates that PNVCL/EC/KET-Eudragit/KET multicomponent fiber mats comprise effective and biocompatible materials for targeted drug delivery