Layla Nabai
Dermatologist pursuing PhD in Wound Healing
Title: Controlled delivery of kynurenic acid: A novel approach to prevention of post-surgical fibrosis
Biography
Biography: Layla Nabai
Abstract
Statement of the Problem: Hypertrophic scars and keloids are devastating fibrotic conditions. Despite advances in knowledge and various therapeutic methods prevention and treatment of these conditions remains a challenge. Our group has previously shown that kynurenic acid (KyA) as a topical formulation reduces hypertrophic scarring in rabbit ear model. In this study we hypothesized that the use of a biocompatible and biodegradable polymer microsphere for controlled slow release of KyA will reduce fibrosis in closed wound in a rat model.
Methods: The FDA approved Poly (lactic-co-glycolic acid) (PLGA) polymer was used to encapsulate KyA. An animal model of wound healing which involves subcutaneous implantation of pre-cut PVA sponges in rat was used to evaluate the in vivo efficacy of the microspheres.
Results: The in vitro experiments revealed a successful encapsulation of KyA (average encapsulation efficiency=80.65±18.49%) and a release profile that showed a gradual release over 35 days following a lag phase for 30 days. Both histological examination and hydroxyproline assay of the samples harvested after 66 days revealed a significant reduction in collagen deposition inside and around the PVA sponge implants loaded with KyA microspheres compared with the PVA alone or loaded with empty microspheres (0.3±0.5, 6.74±2.77, 2.7±0.89 mg collagen/PVA respectively). There was no significant difference between samples collected after 35 days.
Conclusion & Significance: Our data suggests that gradual release of KyA after 30 days can prevent fibrosis in vivo while the lag phase allows normal healing process to occur. This drug delivery system provides a novel approach toward prevention of fibrosis after surgical interventions.