Red blood cell ghosts as promising drug carriers to target wound infections

Hightlights
• We investigated a healing potential of RBCs loaded with cytokine IL-1β and antibiotic.
• We investigated pharmacokinetic properties of IL-1β loaded into RBCs.
• Treatment with loaded RBCs accelerates healing of the infectious wounds.
• RBCs improve pharmacokinetic profiles of IL-1β.

Autologous red blood cell ghosts (RBC ghosts) can carry cytokines to the sites of inflammation. The targeting moiety of the RBC ghosts is associated with the nature of purulent inflammation, where the erythrocytes are phagocyted and encapsulated drugs are released. In the present study we have investigated the healing potential of RBC ghosts loaded with cytokine IL-1β and antibiotic. Additionally, the pharmacokinetic properties of RBC ghosts loaded with IL-1β were studied. 35 Male Wistar rats (250–300 g) were used in the pharmacokinetic study and in a wound infection model where a suspension of Staphylococcus aureus was placed into a surgical cut of the skin and subcutaneous tissue in the femoral region. In order to monitor progression of the wound repair processes, wound swabs or aspiration biopsies were taken for analyses on the 1st–6th days. Wound repair dynamics assessment was based on suppression of S. aureus growth, signs of pain, time of disappearance of pus and infiltration around the wound. Visual observations, as well as microbiological and cytological analysis of wound exudates demonstrated a significant acceleration of healing processes in a group of animals treated with a local injection of IL-1β and ceftriaxone encapsulated into RBC ghosts when compared to the animals treated either with a local or IM injection of free drugs. For the pharmacokinetic study, single IV injections of either free or encapsulated IL-1β were made and the concentration of IL-1β in serum samples and tissue homogenates were determined. Encapsulation in RBC ghosts improved pharmacokinetic profiles of IL-1β by increasing the half-life, reducing its clearance, and increasing the deposition of the drug in the liver, spleen and lungs. These data suggest that RBC ghosts are effective drug carriers for targeted delivery of cytokines to the sites of inflammation, and have a potential for improving the treatment outcomes of purulent diseases.