Encapsulation of ruthenium(II) uracil compounds into chitosan (CS)-polyvinyl alcohol (PVA) electrospun nanofibers: Nanofabrication, characterization, drug release, and anti-diabetic studies

Abstract

Our earlier studies on a leading uracil-Schiff base chelated ruthenium compound, [Ru(H 3 ucp)Cl(PPh 3 )] ( 1 ) (H 4 ucp = 2,6- bis -((6-amino-1,3-dimethyluracilimino)methylene)pyridine) showed it can serve as a candidate metal-based drug in an anti-diabetic animal model. Most recently, we have shown that the structural features of 1 and its derivatives dictate their anti-diabetic mechanism of action. In the pursuit of developing proficient metallopharmaceuticals for diabetes mellitus, the lead metal complex and its analogs were individually incorporated into nanoconfined polymer frameworks to investigate their drug-release profiles and glucose-lowering effects over time in selected cell lines. In particular, chitosan (CS)-polyvinyl alcohol (PVA) electrospun nanofibers (CS-PVA ENFs) containing the different ruthenium uracilimino complexes (Ru) were fabricated by in situ electrospinning. The resultant guest-host nanocomposites were characterized by Scanning Electron Microscopy with Energy-Dispersive X-ray (SEM-EDX) spectroscopy, powder X-ray Diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, and Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). The Ru-CS-PVA ENF nanohybrids exhibited a randomly oriented fiber mat morphology with mean diameters ranging from 119 to 270 nm. Of particular interest is that the drug release rates were significantly faster in acidic media than in physiological pH. The Ru-CS-PVA ENFs showed no cytotoxicity effects and enhanced glucose uptake in both the HepG2 liver and C2C12 skeletal muscle cell lines at 24- and 48-hour treatment periods. Highest ruthenium concentrations of 1.3 and 0.140 mg/L for a specific nanocomposite were attained during drug desorption and intestinal intracellular permeability studies, respectively. These nanocomposites can serve as promising oral drug delivery systems for the treatment of Diabetes Mellitus. • Chitosan (CS)-polyvinyl alcohol (PVA) electrospun nanofibers (CS-PVA ENFs) • CS-PVA-ENFs containing the different ruthenium uracilimino complexes (Ru) • Ru-CS-PVA ENF nanohybrids characterized by various techniques • Ru-CS-PVA ENFs illustrate faster drug release at acidic pH than at pH 7.4 • Nanocomposites showed no in vitro cytotoxicity effects and enhanced glucose uptake