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

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Abstract

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.
LanguageEnglish
Pages477-488
Number of pages12
JournalDrug Delivery and Translational Research
Volume2
Issue number6
Early online date3 Oct 2012
DOIs
StatusPublished - 1 Dec 2012

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Tetracycline
Nanofibers
Anti-Bacterial Agents
Skin
Immersion
Wound Healing
Staphylococcus aureus
Polymers
Fluorescence
Phosphates
Drug Liberation
ethylenevinylacetate copolymer
polycaprolactone
Bacteria
Infection
Pharmaceutical Preparations

Cite this

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title = "Electrospun matrices for localised controlled drug delivery: release of tetracycline hydrochloride from layers of polycaprolactone and poly(ethylene-co-vinyl acetate)",
abstract = "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 beendesigned, prepared as micro/nanofibre layers, and assayed forthe controlled release of the clinically useful antibiotic Tet HClwith potential applications in wound healing and especially incomplicated skin and skin-structure infections. Tet HCl wasalso chosen as amodel drug possessing a good ultraviolet (UV)chromophore and capable of fluorescence together with limitedstability. Tet HCl was successfully incorporated (essentiallyquantitatively at 3 {\%}, w/w) and provided controlled releasefrom multilayered electrospun matrices. The Tet HCl releasetest was carried out by a total immersion method on 2×2 cm2electrospun fibrous mats in Tris or phosphate-buffered salineheated to 37 °C. The formulation PCL/PEVA/PCL with TetHCl in each layer gave a large initial (burst) release followed bya sustained release. Adding a third layer to the two-layeredformulations led to release being sustained from 6 days to morethan 15 days. There was no detectable loss of Tet chemicalstability (as shown by UVand NMR) or bioactivity (as shownby a modified Kirby–Bauer disc assay). Using Tet HClsensitivebacteria, Staphylococcus aureus (ATCC 25923), theTet HCl-loaded three-layered matrix formulations were stillshowing significantly higher antibacterial effects on days 4and 5 than commercially available Antimicrobial SusceptibilityTest Discs of Tet HCl. Electrospinning provides good encapsulationefficiency of Tet HCl within PCL/PEVA/PCL polymersin micro/nanofibre layers which display sustainedantibiotic release.",
author = "Nour Alhusein and Blagbrough, {Ian S.} and {De Bank}, {Paul A}",
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T1 - Electrospun matrices for localised controlled drug delivery: release of tetracycline hydrochloride from layers of polycaprolactone and poly(ethylene-co-vinyl acetate)

AU - Alhusein, Nour

AU - Blagbrough, Ian S.

AU - De Bank, Paul A

PY - 2012/12/1

Y1 - 2012/12/1

N2 - 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 beendesigned, prepared as micro/nanofibre layers, and assayed forthe controlled release of the clinically useful antibiotic Tet HClwith potential applications in wound healing and especially incomplicated skin and skin-structure infections. Tet HCl wasalso chosen as amodel drug possessing a good ultraviolet (UV)chromophore and capable of fluorescence together with limitedstability. Tet HCl was successfully incorporated (essentiallyquantitatively at 3 %, w/w) and provided controlled releasefrom multilayered electrospun matrices. The Tet HCl releasetest was carried out by a total immersion method on 2×2 cm2electrospun fibrous mats in Tris or phosphate-buffered salineheated to 37 °C. The formulation PCL/PEVA/PCL with TetHCl in each layer gave a large initial (burst) release followed bya sustained release. Adding a third layer to the two-layeredformulations led to release being sustained from 6 days to morethan 15 days. There was no detectable loss of Tet chemicalstability (as shown by UVand NMR) or bioactivity (as shownby a modified Kirby–Bauer disc assay). Using Tet HClsensitivebacteria, Staphylococcus aureus (ATCC 25923), theTet HCl-loaded three-layered matrix formulations were stillshowing significantly higher antibacterial effects on days 4and 5 than commercially available Antimicrobial SusceptibilityTest Discs of Tet HCl. Electrospinning provides good encapsulationefficiency of Tet HCl within PCL/PEVA/PCL polymersin micro/nanofibre layers which display sustainedantibiotic release.

AB - 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 beendesigned, prepared as micro/nanofibre layers, and assayed forthe controlled release of the clinically useful antibiotic Tet HClwith potential applications in wound healing and especially incomplicated skin and skin-structure infections. Tet HCl wasalso chosen as amodel drug possessing a good ultraviolet (UV)chromophore and capable of fluorescence together with limitedstability. Tet HCl was successfully incorporated (essentiallyquantitatively at 3 %, w/w) and provided controlled releasefrom multilayered electrospun matrices. The Tet HCl releasetest was carried out by a total immersion method on 2×2 cm2electrospun fibrous mats in Tris or phosphate-buffered salineheated to 37 °C. The formulation PCL/PEVA/PCL with TetHCl in each layer gave a large initial (burst) release followed bya sustained release. Adding a third layer to the two-layeredformulations led to release being sustained from 6 days to morethan 15 days. There was no detectable loss of Tet chemicalstability (as shown by UVand NMR) or bioactivity (as shownby a modified Kirby–Bauer disc assay). Using Tet HClsensitivebacteria, Staphylococcus aureus (ATCC 25923), theTet HCl-loaded three-layered matrix formulations were stillshowing significantly higher antibacterial effects on days 4and 5 than commercially available Antimicrobial SusceptibilityTest Discs of Tet HCl. Electrospinning provides good encapsulationefficiency of Tet HCl within PCL/PEVA/PCL polymersin micro/nanofibre layers which display sustainedantibiotic release.

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VL - 2

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EP - 488

JO - Drug Delivery and Translational Research

T2 - Drug Delivery and Translational Research

JF - Drug Delivery and Translational Research

SN - 2190-393X

IS - 6

ER -