In Vitro and In Vivo Antimicrobial Activity of Antibiotic‐Conjugated Carriers with Rapid pH‐Responsive Release Kinetics

Abstract

Two representative antibiotics, cephradine (CP) and moxifloxacin (MX), are covalently conjugated with a β‐cyclodextrin (β‐CD)‐based carrier via pH‐responsive 1‐methyl‐2‐(2′‐carboxyethyl) maleic acid amide (MCM) linkers with excellent conjugation efficiency via simple mixing. At pH 5.5, 90% and 80% of the CP and MX, respectively, are released from the carriers within 30 min, in contrast with the much‐delayed release profile at pH 7.4. The in vitro inhibitory effect of β‐CD–MCM–CP on the growth of Staphylococcus aureus is significantly lower than that of free CP at pH 7.4, but it reaches the level of free CP at pH 5.5. Moreover, S. aureus develops significant CP resistance after pretreatment with free CP, whereas the initial CP sensitivity is maintained after pretreatment with β‐CD–MCM–CP at pH 7.4. However, β‐CD–MCM–MX exhibits no such pH‐responsive activity against Bacteroides fragilis, probably due to the insufficient stability of the MX conjugation at pH 7.4. In nondiabetic and diabetic mouse models, β‐CD–MCM–CP significantly reduces the subcutaneous abscess scores and the bacterial counts in the abscess, although this represents only a marginal improvement in antimicrobial activity compared to free CP.

A Self‐Powered Wound Dressing Based on “Lock‐ON/OFF” Drug Release Combined Electric Stimulus Therapy for Accelerated Infected Wound Healing

“…The stimulus-response drug carrier can automatically adjust the drug release rate while achieving the drug-targeted freedom under the stimulation of exogenous or human environmental factors. [12] Currently, traditional intelligent response systems, such as pH, temperature, electric-field (EF), and photochemical response, although it has the characteristics of brilliant response drug release, due to the hydrophilicity of antibiotic drugs, it will still be released by the concentration gradient when the stimulus conditions are not applied, causing drug resistance problems. [12,13] Thus, realizing the complete shutdown of the intelligent response switch is a crucial problem in preventing drug leakage under non-stimulus conditions.…”

“…[12] Currently, traditional intelligent response systems, such as pH, temperature, electric-field (EF), and photochemical response, although it has the characteristics of brilliant response drug release, due to the hydrophilicity of antibiotic drugs, it will still be released by the concentration gradient when the stimulus conditions are not applied, causing drug resistance problems. [12,13] Thus, realizing the complete shutdown of the intelligent response switch is a crucial problem in preventing drug leakage under non-stimulus conditions. Meanwhile, the main reason for the leakage of drugs under normal conditions is that the diffusion driving force under the concentration gradient is greater than the bondage force of the drug carrier.…”

A pH-responsive supramolecular antibacterial agent based on host–guest chemistry

“…Inspired by the effective application of microenvironment-responsive nanomaterials in tumor therapy, a variety of antibacterial platforms that respond to the environment at the infection site for anti-infection therapy have been constructed by scientists. 7–14 The microenvironment of the inflammatory infection site is different from that of normal tissues, including elevated contents of hydrolytic enzymes and toxins, elevated local temperatures, lower oxygen contents, and lower pH values. 15–17 The acidic infection microenvironment can serve as an “endogenous switch” for stimulating responsive drug delivery due to anaerobic glycolysis.…”