Development of a Topical 48-H Release Formulation as an Anti-scarring Treatment for Deep Partial-Thickness Burns
The purpose of this study was to develop pirfenidone (PF) ointment formulations for a dose finding study in the prophylactic treatment of deep partial-thickness burns in a mouse model. A preformulation study was performed to evaluate the solubility of PF in buffers and different solvents and its stability. Three different formulations containing 1, 3.5, and 6.5% w/w PF were prepared and optimized for their composition for testing in mice. Optimized formulations showed promising in vitro release profiles, in which 20–45% of PF was released in the first 7 h and 70–90% released within 48 h. The rheological properties of the ointment remained stable throughout storage at 25 ± 2°C/60% RH. Animal studies showed treatments of burn wounds during the inflammatory stage of wound healing with PF ointments at different drug concentrations had no adverse effects on reepithelization. Moreover, 6.5% PF ointment (F3) reduced the expression of pro-inflammatory cytokines IL-12p70 and TNFα. This study suggests that hydrocarbon base ointment could be a promising dosage form for topical delivery of PF in treatment of deep partial-thickness burns.
KEY WORDSpirfenidone ointment formulations burn treatment deep partial-thickness burn mice
RD performed this study at the US Army Institute of Surgical Research during her sabbatical leave from the University of Pavia, Italy. Her stipend was supported by an appointment to the Postgraduate Research Participation Program at the US Army Institute of Surgical Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and US Army Medical Research and Materiel Command (USAMRMC). This work was supported in part through the Congressionally Directed Medical Research Programs, USAMRMC W81XWH-15-2-0083, and the Naval Medical Research Center’s Advanced Medical Development program (MIPR N3239815MHX040).
Compliance with Ethical Standards
This study has been conducted in compliance with the Animal Welfare Act, the implementing Animal Welfare Regulations, and the principles of the Guide for the Care and Use of Laboratory Animals.
Conflict of Interest
The authors declare that they have no conflict of interest.
The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
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