| Περίληψη: | Burn injury is a serious damage of skin and other tissues that can lead to severe morbidity and significant mortality. Pathological post-burn scarring can lead to severe functional impairment, psychological morbidity, and costly long-term healthcare [1, 2]. Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone, PF) is a broad-spectrum agent having anti-fibrotic and anti-inflammatory activities. PF presents a wide range of therapeutical applications and its safety and efficacy has been assessed for several diseases such as idiopathic pulmonary fibrosis, neurofibromatosis, chronic hepatitis, and cardiomyopathy. PF therapeutic activity is attributed to its efficacy in reducing fibroblast proliferation, decreased secretion of the fibrosis-associated cytokines, decreased biosynthesis of extracellular matrix, and decreased accumulation of inflammatory cells [3, 4]. The aim of project is to exploit nanotechnological approaches in order to develop a sustained-release PF formulation for treating deep partial thickness burn (DPTBs). The main goal was to encapsulate PF into nanoparticulate systems and nanofibers exploiting few cutting-edge process technologies, as microfluidic and electrospinning in order to achieve sustained-release formulations. Both the formulations are intended for topical application on cutaneous wound.
Material & Methods - PF loaded nanoparticles (NPs) were prepared by a biodegradable and biocompatible polymer, PLGA (poly lactic-co-glycolic acid, 75:25 6A 90 kDa). Different aqueous buffers, at specific pH and molarity values were investigated to maximize the encapsulation efficiency of PF into NPs. NPs were characterized in term of size, size distribution and morphology by Transmission Electron Microscopy (TEM) and of surface features by Atomic Force Microscopy (AFM). Moreover, the in vitro release and stability of PF loaded NPs were investigated. The proper selection of process parameters for NPs production were assessed by Design of Experiments (DoE). PF loaded nanofibers (NFs) were prepared by NANON-01A instrument and they were characterized by Scanning Electron Microscopy (SEM) for size, size distribution, pores, porosity and fiber orientation. Electrospun specimens (dog bone shape 80 x 10 x 4 mm, ASTM D882) were analyzed by tensile tester for tensile strength and deformation behavior. The in vitro release of the most promising formulations has been performed in phosphate buffer saline (PBS) at 34 ±2°C; following cytocompatibility test on fibroblast cell lines was evaluated.
Results - Various pH and molarity of aqueous buffers in microfluidic-assisted technology for NPs preparation were optimized to achieve the highest encapsulation efficiency. TEM images showed NPs with spherical shape and homogenous size. Tailored size and polydispersity index were < 200 nm and < 0.3, respectively. Regarding NFs, different organic solvent mixtures were selected to obtain suitable fiber size, size distribution and fiber orientation, as well as porosity. PF loaded NPs and NFs demonstrated a sustained-release profile in PBS at 34 ±2°C and good biocompatibility.
Conclusion - Both the exploited nanotechnological approaches have turned out promising formulations to achieve PF sustained-release. The in vitro release study of optimized formulations will be further evaluated in simulated wound fluid (SWF) and nanoparticle cellular uptake will be assessed by confocal microscopy.
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