At present, some bacteria have developed significant resistance to almost all available antibiotics. One of the reasons that cannot be ignored is long-term exposure of bacteria to the sub-minimum inhibitory concentration (MIC) of antibiotics. Therefore, it is necessary to develop a targeted antibiotic delivery system to improve drug delivery behavior, in order to delay the generation of bacterial drug resistance. In recent years, with the continuous development of nanotechnology, various types of nanocarriers that respond to the infection microenvironment, targeting specific bacterial targets, and targeting infected cells, and so on, are gradually being used in the delivery of antibacterial agents to increase the concentration of drugs at the site of infection and reduce the side effects of drugs in normal tissues. Here, this article describes in detail the latest research progress on nanocarriers for antimicrobial, and commonly used targeted antimicrobial strategies. The advantages of the combination of nanotechnology and targeting strategies in combating bacterial infections are highlighted in this review, and the upcoming opportunities and remaining challenges in this field are rationally prospected.
Cocrystal (CC) and coamorphous (CM) techniques have become green technologies to improve the solubility and bioavailability of water-soluble drugs. In this study, hot-melt extrusion (HME) was employed to produce CC and CM formulations of indomethacin (IMC) and nicotinamide (NIC) due to its advantages like solvent-free and large-scale manufacturing. Interestingly, for the first time, IMC−NIC CC and CM were selectively prepared depending on the barrel temperatures of HME at a constant screw speed of 20 rpm and a feed rate of 1.0 g/min. IMC−NIC CC was obtained at 105−120 °C, IMC−NIC CM was produced at 125−150 °C, and the mixture of CC and CM was obtained between 120 and 125 °C (like a door switch of CC and CM). SS NMR combined with RDF and E bind calculations revealed the formation mechanisms of CC and CM, where strong interactions between heteromeric molecules formed at lower temperatures favored periodic molecular organization of CC, whereas discrete and weak interactions formed at higher temperatures promoted disordered molecular arrangement of CM. Additionally, IMC−NIC CC and CM showed enhanced dissolution and stability over crystalline/amorphous IMC. This study provides an easyto-operate and environmentally friendly strategy for the flexible regulation of CC and CM formulations with different properties through modulation of the barrel temperature of HME.
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