Mehran Alavi - Department of Biological Sciences, Faculty of Science, University of Kurdistan, Kurdistan, Sanandaj, Iran Nanobiotechnology Department, Faculty of Innovative Science and Technology, Razi University, Kermanshah, Iran
Michael Hamblin - Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, ۲۰۲۸, South Africa Wellman Centre for Photomedicine, Massachusetts General Hospital, Boston, MA ۰۲۱۱۴, USA Department of Dermatology, Harvard
Ermia Aghaie - High Performance Powertrain Materials Laboratory, School of Engineering, University of British Columbia – Okanagan, Kelowna, V۱V ۱V۷, Canada
Seyed Ali Reza Mousavi - Department of Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA ۹۲۰۳۷; Howard Hughes Medical Institute, The Scripps Research Institute, La Jolla, CA ۹۲۰۳۷
Mohammad Hajimolaali - Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

There are up to one million secondary metabolites found in plant species, some of which may have desirable therapeutic activities. Among these secondary metabolites, catechin, gallic acid, and epigallocatechin-۳-gallate are natural phenolic compounds with promising antioxidant and antibacterial activity. However, these compounds have disadvantages of poor solubility and low bioavailability in physiological conditions, along with side effects in patients. Therefore new strategies could rely on formulations with other synthetic and natural materials. Nanoformulations of secondary metabolites could be new efficient strategies to treat many chronic bacterial infections. Combinations and conjugates of catechin, gallic acid, and epigallocatechin-۳-gallate with various antibiotics could reduce the dose of these compounds, increase their antibacterial activity, and decrease cytotoxicity against healthy cells. For instance, a smart combination of two or more secondary metabolites may improve therapeutic applications in physiological conditions. In this regard, the growth of antibiotic-resistant bacteria, specifically multidrug-resistant bacteria with overexpression of efflux pumps and expression of the penicillinase enzyme, has been inhibited significantly. According to recent investigations, this review will discuss the advances and challenges of new micro and nanoformulations of these natural products.

Secondary metabolites, Natural phenolic compounds, Low bioavailability, Antibacterial Activity, Nanomaterials, Combination therapy