A soft skin adhesive (SSA) patch for extended release of pirfenidone in burn wounds
Case Study
Eugene P. Chung1,2, Jesse Q. Nguyen1, Tobias Tellkamp-Schehr3, Katja Goebel3, Anita Ollek3, Cliff Krein3, Adrienne R. Wells1,4, Eliza A. Sebastian1, Anja Goebel3, Svenja Niese3 and Kai P. Leung1,*
- Combat Wound Care Group, US Army Institute of Surgical Research, JBSA, Fort Sam Houston, TX 78234, USA
- Department of Bioengineering, Rice University, Houston, TX 77005, USA
- Labtec GmbH, Raiffeisenstrasse 4, 40764 Langenfeld, Germany; a.ollek@adhexpharma.com (A.O.); c.krein@adhexpharma.com (C.K.); s.niese@adhexpharma.com (S.N.)
- MicRoN Core, Harvard Medical School, Boston, MA 02215, USA
*Correspondence: kai.p.leung.civ@health.mil
Abstract: As much as half or more of deep partial-thickness burn wounds develop hypertrophic scarring and contracture. Once such scarring and contracture have formed, treatments are only minimally effective. Pirfenidone (Pf), indicated for treatment of idiopathic pulmonary fibrosis, is an anti-inflammatory and anti-fibrotic small molecule that potentially can be repurposed as a preventative against scarring in burn wounds. We present a drug-in-matrix patch with a soft skin adhesive (SSA) wound-contacting layer for multiday drug delivery of Pf into burn wounds at the point of injury. Our patch construction consists of an SSA adhesive layer (DuPont™ Liveo™ MG 7-9850 Soft Skin Adhesive, DuPont, Wilmington, DE, USA) for wound fixation; an acrylic copolymer drug matrix (DURO-TAK 87-2852, Henkel, Düsseldorf, Germany) as the drug (Pf) reservoir; and an outermost protective polyurethane backing. By employing a drug-in-matrix patch design, Pf can be loaded as high as 2 mg/cm2. Compared to the acrylic copolymer adhesive patch preparations and commercial films, adding an SSA layer markedly reduces skin-stripping observed under scanning electron microscopy (SEM). Moreover, the addition of varying SSA thicknesses did not interfere with the in-vitro release kinetics or drug permeation in ex-vivo porcine skin. The Pf patch easily can be applied onto and removed from deep partial-thickness burn wounds on Duroc pigs. Continuous multiday dosing of Pf by the patches (>200 µg/cm2/day) reduced proinflammatory biomarkers in porcine burn wounds. Pf patches produced by the manual laboratory-scale process showed excellent stability, maintaining intact physical patch properties and in-vitro biological activity for up to one year under long-term (25°C at 60% RH) and 6 months under accelerated (40°C at 75% RH) test conditions. To manufacture our wound safe-and-extended-release patch, we present scale-up processes using a machine-driven automated roll-to-roll pilot-scale coater.
This innovative drug-in-matrix patch offers a promising solution for burn wound treatment with extended release of Pirfenidone.
To continue reading the full journal article as it appeared in MDPI Pharmaceutics 2023, volume 15, issue 7, download the PDF.