Electrospun matrices for localised controlled drug delivery: release of tetracycline hydrochloride from layers of polycaprolactone and poly(ethylene-co-vinyl acetate)

We report the controlled release of tetracycline (Tet)
HCl from a three-layered electrospun matrix for the first time.
Five formulations of electrospun poly-ε-caprolactone (PCL)
and poly(ethylene-co-vinyl acetate) (PEVA) have been
designed, prepared as micro/nanofibre layers, and assayed for
the controlled release of the clinically useful antibiotic Tet HCl
with potential applications in wound healing and especially in
complicated skin and skin-structure infections. Tet HCl was
also chosen as amodel drug possessing a good ultraviolet (UV)
chromophore and capable of fluorescence together with limited
stability. Tet HCl was successfully incorporated (essentially
quantitatively at 3 %, w/w) and provided controlled release
from multilayered electrospun matrices. The Tet HCl release
test was carried out by a total immersion method on 2×2 cm2
electrospun fibrous mats in Tris or phosphate-buffered saline
heated to 37 °C. The formulation PCL/PEVA/PCL with Tet
HCl in each layer gave a large initial (burst) release followed by
a sustained release. Adding a third layer to the two-layered
formulations led to release being sustained from 6 days to more
than 15 days. There was no detectable loss of Tet chemical
stability (as shown by UVand NMR) or bioactivity (as shown
by a modified Kirby–Bauer disc assay). Using Tet HClsensitive
bacteria, Staphylococcus aureus (ATCC 25923), the
Tet HCl-loaded three-layered matrix formulations were still
showing significantly higher antibacterial effects on days 4
and 5 than commercially available Antimicrobial Susceptibility
Test Discs of Tet HCl. Electrospinning provides good encapsulation
efficiency of Tet HCl within PCL/PEVA/PCL polymers
in micro/nanofibre layers which display sustained
antibiotic release.