Dual loading of Nigella sativa oil-atorvastatin in chitosan–carboxymethyl cellulose nanogel as a transdermal delivery system

Abstract

Both Nigella sativa oil and atorvastatin possess anti-inflammatory, immunomodulatory, antioxidant, and antibacterial properties that benefit wound healing. In this work, chitosan–carboxymethyl cellulose was loaded on N. sativa oil to synthesize oil nanogel (ONG) which was later used to load with atorvastatin to obtain atorvastatin-oil nanogel (ATONG). Evaluation of the particle size of ONG and ATONG proved the average of 172 and 193 nm, and their surface charges were found to be 32.2 and 34.7 mV, respectively. Transmission electron microscopy of the sample showed that the particles had homogeneous size distributions with spherical structures. Moreover, drug loading efficiency, drug release, and stability of ATONG were investigated, and their results confirmed the appropriate loading and release of atorvastatin. Cytotoxicity evaluation demonstrated that ATONG can safely release atorvastatin intracellularly in fibroblasts. Results from in vitro skin permeation of ONG and ATONG also revealed that the nanogels (NGs) has proper flux through the skin layers. The in vitro wound closure assay for ATONG verified the proliferation and migration capabilities of fibroblasts, confirming the positive effect on wound-healing applications. In scratch model of fibroblasts, the treatment with ATONG resulted in an increase in the expression of the FGF2, TGF-β1, and VEGF genes involved in fibroblast proliferation and migration aimed at wound healing (p < .001). ATONG, also demonstrated bactericidal effects against Staphylococcus, S. aureus, and S. epidermidis species. Based on the results, ONG and ATONG exhibited great potential to be used as a transdermal drug carrier and skin wound healing NG, respectively.