Mucoadhesive, Antibacterial, and Reductive Nanogels as a Mucolytic Agent for Efficient Nebulized Therapy to Combat Allergic Asthma

Abstract

Asthma is an intractable disease involving the infiltration of inflammatory cells and mucus plugging. Despite small molecular mucolytics having the ability to break the disulfide bonds of mucins, offering a potential way to overcome the airflow obstruction and airway infection, these mucolytics have limited therapeutic effects in vivo. Therefore, in this work, arginine-grafted chitosan (CS-Arg) is ionically cross-linked with tris(2-carboxyethyl)phosphine (TCEP) to obtain nanogels as a mucolytic agent. The positively charged nanogels effectively inhibit the formation of large aggregates of mucin in vitro, probably thanks to the formation of an ionic interaction between CS-Arg and mucin, as well as the breakage of disulfide bonds in mucin by the reductive TCEP. Moreover, the nanogels show good cytocompatibility at concentrations up to 5 mg mL −1 , exhibiting effective inhibitory effects against the proliferation of both Staphylococcus aureus and Escherichia coli at 5 mg mL −1 . After the administration of the nanogels by nebulization into a Balb/c mouse model with allergic asthma, they can efficiently reduce the mucus obstruction in bronchioles and alveoli and relieve airway inflammation. Therefore, these CS-Arg/TCEP nanogels potentially represent a promising mucolytic agent for the efficient treatment of allergic asthma and other muco-obstructive diseases.

3D Adsorption‐Mediator Network Polymer Binders Improve Redox Kinetics and Flame Retardant Performance for High Loading Lithium–Sulfur Batteries

“…Compared with PEI, three different characteristic peaks in N 1s spectra at 398. [31] The mentioned experimental results demonstrated that Arg successfully conducted the amidation reaction with PEI. Subsequently, the mediator cross-linker TCEP was added to the system, and the 3D cross-linked binder PAT was obtained.…”

Ultra-stiff and tough hydrogels based on small but strong hydrophobic associations via a low-reactive hydrophilic monomer

“…Mouse embryonic fibroblast (NIH-3T3) cells received from Chen's group 41 were used to evaluate the in vitro cytotoxicity of the hydrogel. First, the test extract was prepared by immersing the hydrogel in DMEM (3 cm 2 mL −1 ) containing 10% FBS, 100 μg mL −1 streptomycin and penicillin, and 1% l -glutamine at 37 °C for 24 h. The extract (100%) was diluted with DMEM to 10% and 1% of the original.…”

Exploring the Potential of Nanogels: From Drug Carriers to Radiopharmaceutical Agents

“…Zhao et al developed a nanogel as a mucolytic agent for the treatment of asthma. [81] This nanogel, which consists of argininegrafted chitosan and tris(2-carboxyethyl)phosphine (TCEP), can be administered via a nebulizer. The nanogel prevented the aggregation of mucin, i.e., the cause of mucus clogging in the nasal cavity and elsewhere, via two types of actions, i.e., the electrostatic interaction at the chitosan moiety and disulfide bond cleavage by TCEP, which effectively inhibited the growth of two bacterial species.…”