Natural product-based nanomedicines for wound healing purposes: therapeutic targets and drug delivery systems

Natural product-based nanomedicines for wound healing purposes: therapeutic targets and drug delivery systems Marziyeh Hajialyani,1 Devesh Tewari,2 Eduardo Sobarzo-Sánchez,3,4 Seyed Mohammad Nabavi,5 Mohammad Hosein Farzaei,1 Mohammad Abdollahi6 1Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; 2Department of Pharmaceutical Sciences, Faculty of Technology, Kumaun University, Nainital, India; 3Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Spain; 4Instituto de Investigación e Innovación en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Chile; 5Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran; 6Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS) and Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Abstract: Wound healing process is an intricate sequence of well-orchestrated biochemical and cellular phenomena to restore the integrity of the skin and subcutaneous tissue. Several plant extracts and their phytoconstituents are known as a promising alternative for wound healing agents due to the presence of diverse active components, ease of access, and their limited side effects. The development of nanotechnological methods can help to improve the efficacy of different therapeutics as well as herbal-based products. Here, we present a review of the efficacy of the plant based-nanomaterials in the management of wounds and discuss the involved therapeutic targets. For this purpose, a profound search has been conducted on in vitro, in vivo, and/or clinical evidences evaluating the efficacy and pharmacological mechanisms of natural product-based nanostructures on different types of wounds. Different pharmacological targets are involved in the wound healing effects of herbal-based nanostructures, including suppressing the production of inflammatory cytokines and inflammatory transduction cascades, reducing oxidative factors and enhancing antioxidative enzymes, and promoting neovascularization and angiogenic pathways through increasing the expression of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor. Moreover, nanostructure of plant extracts and their phytochemicals can enhance their bioavailability, control their release in the form of sustained delivery systems to the wound site, and enhance the permeability of these therapeutics to the underlying skin layers, which are all necessary for the healing process. Overall, various plant extracts and their natural compounds, used in nanoformulations, have demonstrated high activity in the management of wounds and thus can be assumed as future pharmaceutical drugs. Keywords: nanomedicine, nanoparticle, nanofiber, natural product, medicinal plants, phytochemicals, herbal products, hydrogels, nanoemulsion, electrospinning, wound healing, wound dressing, nanostructure