Q-Starch as a carrier for PIP₃ controlled release wound healing

According to the Wound Healing Society, a wound is the result of disruption in a normal anatomic structure and function, which can be caused by applying mechanical force, thermal alternations, or biological changes at the wound site. The wound healing process has been well studied and includes 4 main stages, which lasts 8-12 weeks in acute wound, and longer time in chronic wounds. A malfunction in one of the stages of wound healing can cause a chronic wound and lead to local and systematic infections, organ amputation and even death. Therefore, it is necessary to heal the wound in the shortest possible time, thereby preventing exposure to the environment and reducing the risk of contamination.

Phosphatidylinositol-3,4,5-trisphosphate (PIP3) was found to take an active part in the wound healing processes including cell migration, transcription and proliferation via phosphoinositide 3 kinase (PI3K) pathway. Hence, our hypothesis is that Integrating PIP3 in a drug delivery system accelerates wound healing process.

The delivery system of the PIP3 is based on a modified Quaternized Starch (Q-Starch) as a cationic carrier which enables to overcome the electrostatic repulsion between the negative charges of the phosphate groups in the PIP3 to the cellular membrane. The Q-starch has been well explored in our lab and found suitable as a carrier for small interference RNA (siRNA), mRNA and more. So far, the Q-Starch/PIP3 complexes were prepared in a self-assembly formation and analyzed using DLS, ζ-potential, Nano Sight, AFM and Cryo-TEM, resulting a nanometric size complex suitable for drug delivery. In addition, the cellular uptake of the complex to the membrane was observed at different time intervals by fluorescent labeling of the Q-Starch and its tracking using a confocal microscope.

In vitro study of cells’ migration was performed on a monolayer of HaCat keratinocyte cell line, using scratch assay and transwell assay methods. The results demonstrated a faster migration towards closure of the scratch in cells in which the Q-Starch/PIP3 complexes were added, compared to control groups. In-vivo experiments are been held in order to evaluate the effect of complexes on the wound healing process.