Up to one million secondary metabolites are found in plant species, some of which may have desirable therapeutic activities. Among these secondary metabolites, catechin, gallic acid, and epigallocatechin-3-gallate are natural phenolic compounds with promising antioxidant and antibacterial activity. However, these compounds have disadvantages of poor solubility, low bioavailability in physiological conditions, and 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-3-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.
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