PEGylated Self-Assembled Nano-Bacitracin A: Probing the Antibacterial Mechanism and Real-Time Tracing of Target Delivery in Vivo
2018
Although nano-self-assemblies of hydrophobic-modified bacitracin A with poly(d,l-lactic-co-glycolic acid) (PLGA) (nano-BAPLGA) have demonstrated promising antibacterial activities, the application of nano-BAPLGA was severely compromised by low water solubility. In this study, a series of PEGylated PLGA copolymers were selected to conjugate with the N-terminus of bacitracin A to construct PEGylated self-assembled nano-BAs and to further develop nano-self-assemblies of bacitracin A with strong antibacterial potency and high solubility. Compared with nano-BAPLGA, all PEGylated nano-BAs, except nano-BA5k, exhibited strong antibacterial efficiency against both Gram-positive and Gram-negative bacteria by inducing loss of cytoplasmic membrane potential, membrane permeabilization, and leakage of calcein from artificial cell membranes. Studies elucidating the underlying mechanism of PEGylated nano-BAs against Gram-negative bacteria indicated that the strong hydrophobic and van der Waals interactions between PLGA a...
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