Design, synthesis and medical prospects of electrospun molecularly imprinted fibers.

The current study describes fabrication of molecularly imprinted (MI) electrospun nanofibers of average diameter 500 nm for controlled delivery of two templates; ferulic acid (FA) and khellin. Polycaprolactone (PCL) was used as supporting matrix in fiber preparation while polyallylamine (PAM) was added to provide molecular recognition sites for the template. The preparation of MI fibers was optimized using design of experiments (DoE). For FA fibers, a fractional factorial deign was used to screen different factors involved in the electrospinning process and it was found that FA and PAM concentration; in addition to PCL concentration were significant. These two variables were used to create a central composite design to optimize fiber diameter. Control fibers were prepared by directly loading ferulic acid into the fiber matrix without PAM. In vitro release studies revealed that MI fibers had more controlled release of FA compared to control fibers. DoE were also used to optimize the diameter of khellin MI fibers. In vitro release studies for khellin MI fibers did not show any significant difference when compared to control fibers. MTT assay was conducted to assess the cytotoxicity of MI fibers against mouse melanoma B16F10 cell lines. FA fibers were well-tolerated by the cells up to a concentration of 250 µg/ml, while khellin fibers showed no cytotoxicity up to a concentration of 125 µg/ml. On the other hand, the non-medicated fibers prepared with only PCL/PAM were safe up to 500 µg/ml, suggesting that the cytotoxicity observed at higher concentration of the MI fibers is due to the effect of FA or khellin. The MI fibers were then subjected to ex-vivo skin permeation studies using vertical Franz diffusion cell with Sprague Dawley male rats back skin. After 24 h, the percentage of permeated drug was 12.71 ± 0.05% for FA and 22.99 ± 0.04% for Khellin.