Modeling the permeability of multiaxial electrospun poly(ε-caprolactone)-gelatin hybrid fibers for controlled doxycycline release

•We form multiaxial fibers using gelatin and poly(ε-caprolactone) in a common solvent in micrometer size.•We evaluated the cell compatibility using human adipocyte stem cells.•Using doxycycline as a model drug, we evaluated the effect of layering and polymer selection on release profile.•We used a novel permeability based modeling to get better insight into regulating fiber characteristics.•Our permeability approach helps in designing fibers with needed drug release profile.

Recent advances in electrospinning allow the formation of multiple layers of micro and nanosize fibers to regulate drug/therapeutic agent release. Although there has been significant progress in fiber formation techniques and drug loading, fundamental models providing insights into controlling individual permeabilities is lacking. In this regard, we first explored forming coaxial hybrid fibers from hydrophobic poly(ε-caprolactone) (PCL) and hydrophilic gelatin (GT) in three different configurations, and the release of hydrophilic doxycycline (Dox) at 37 °C over five days. Triaxial fibers were also formed with a GT layer between PCL/GT layers. Fibers were analyzed for fiber thickness, matrix porosity and thickness, surface morphologies, internal structures, stability in hydrated condition, viability and attachment of human adipocyte stem cells (hASC). Formed fibers were 10-30 μm in diameter. hASC were viable, and showed attachment. Various release profiles were obtained from these fibers based on the combination of the core and shell polymers over five days. Using fiber characteristics and release profiles from each configuration, we obtained the overall permeability using Fick's first law and then individual layer permeability using resistance in series model. Calculated overall permeability showed dependency on fiber thickness and partition coefficient of the drug in the region where it was loaded. Our modeling approach helps in optimizing the electrospinning process, drug loading, and polymer solution configuration in regulating controlled release of a drug.