Chitosan-based electrospun nanofibers mats reinforced with phenytoin-loaded PLGA/Lecithin nanoparticles as potential wound dressings

摘要

Introduction: Fabrication of wound dressings as electrospun nanofibers has privileged the older traditional films in cell proliferation, dermal fibroblasts spreading and consequently wound healing rate. This is due to the capability of producing well controlled nanofibrous dressings with precise dimensions and higher porosity through electrospinning. Chitosan is one of the most convenient biomaterials for wound dressings' fabrication owing to its wide spectrum antibacterial, skin regenerating and wound healing abilities. However, chitosan should be blended with other biocompatible polymers such as polyethylene oxide to be easily electrospun. Phenytoin; a member of barbiturate drugs, has shown a good wound healing activity through increasing the fibroblasts proliferation and collagen deposition. This study aims at preparing PLGA and PLGA/Lecithin nanoparticles loaded with the water insoluble phenytoin base to be easily dispersed within the aqueous electrospinning solution of chitosan and polyethylene oxide (CS/PEO). Material and Methods: PLGA nanoparticles loaded with phenytoin was prepared through nanoprecipitation as reported previously. Afterwards, a portion of the freeze dried drug-loaded nanoparticles was coated with lecithin through thin film hydration technique. Phenytoin-loaded PLGA and PLGA/Lecithin nanoparticles were added each separately to CS/PEO electrospinning solution. Each solution was electrospun to obtain the corresponding nanofibrous mat. Phenytoin release profile was tested from both nanofibers. Finally, the nanofibers were punched into 0.9 mm circular patches, sterilized and tested on mice wounds to observe the wound area over several time points before carrying out histological studies. Results and Discussion: Figure 1 shows that lecithin coating of PLGA nanoparticles showed enhancement in phenytoin release rate when compared to uncoated PLGA nanoparticles. It was also observed that 100 % release of phenytoin from lecithin coated PLGA nanoparticles was achieved after only 9 days, while only about 30% phenytoin was released from the uncoated PLGA nanoparticles ater 12 days. The developed CS/PEO nanofibers incorporating phenytoin-loaded PLGA/lecithin nanoparticles were tested on mice and compared with the corresponding non-reinforced nanofibers. To test the effect of the sustained release of phenytoin from the nanofibers, the experiment was carried out along 10 days, and it can be inferred from the images in Figure 2 that after 10 days the phenytoin has enhanced the wound healing when compared to the phenytoin-free nanofibers. Conclusion: Lecithin coating in PLGA nanoparticles enhanced the drug release when compared to the uncoated counterparts, thus this formula can be further studied as a reliable wound dressing. The nanofibers patches reinforced with phenytoin-loaded PLGA/lecithin nanoparticles were tested on mice and showed noticeable wound healing effect when compared to their non-reinforced counterparts.