Sprayable Antibacterial Hydrogels by Simply Mixing of Aminoglycoside Antibiotics and Cellulose Nanocrystals for the Treatment of Infected Wounds

Abstract

Antibiotic hydrogels with sustained release profiles are recognized as promising candidates to treat local bacterial infections with reduced adverse effects. However, it still remains challenging for clinical translation of these antibiotic gels due to safety concern of gel ingredients, complicated synthesis and fabrication procedures, and unsatisfactory rheological properties for practical uses in vivo. Herein, the preparation of a type of sprayable hydrogels by ionic interactions between aminoglycosides and cellulose nanocrystals (CNC) is proposed for the treatment of local infections such as bacteria-infected wounds. The CNC-based hydrogels are applicable for all kinds of aminoglycoside antibiotics and show excellent gel stability and rheological behaviors such as shear thinning and fast self-healing, allowing facile administration by injection or spraying. The hydrogels exhibit efficient antibacterial activity both in vitro and in vivo, and accelerate bacteria-infected wounds by spraying on the infected area. The proposed hydrogels by simply mixing of aminoglycosides and CNC provide great prospects for clinical translation in the treatment of local infections.

Nanocellulose-based hydrogels for drug delivery

“…136 An interesting example of this technique is the development of a sprayable antibacterial hydrogel by blending aminoglycosides with CNCs, without the need for additional complex chemical modifications. 137 A stable hydrogel structure is formed by the electrostatic interactions between the aminoglycosides and cellulose surface groups. By adjusting the amount of CNCs added, the rheological properties of the hydrogel can be precisely tuned to switch between sprayable and injectable application scenarios (Fig.…”

Preparation and Application of Biomass-based Sprayable Hydrogels

“…The abundance of hydroxyl groups and negative charges on the surface of cellulose nanocrystals (CNC) could further introduce other functions through chemical conjugation or electrostatic absorption [91][92][93] .…”

“…Li et al [92] prepared an antibiotic hydrogel via ionic interactions between the sulfate groups on CNC and the amine groups on aminoglycosides. The sprayed hydrogels exhibited high cohesiveness, allowing high adhesion on vertical surfaces because of the intermolecular hydrogen bonding between the abundant hydroxyl groups on the CNC.…”

“…Aminoglycoside antibiotics are a class of antibiotics that contain multiple amine groups in their structure, whose antibacterial effect is achieved by transport across cell membranes and by binding to bacterial ribosomes to disrupt protein synthesis; they are recognized as effective broad-spectrum antibacterial drugs [136,138] . Li et al [92] designed a sprayable hydrogel composed of CNC and aminoglycoside antibiotics. The hydrogel was prepared by ionic interactions between CNC and tobramycin (TOB), and the rheological properties of the spray were altered by adjusting the concentration of CNC.…”

An injectable all-small-molecule dynamic metallogel for suppressing sepsis

“…20,21 Rational design and facile fabrication strategies that enable control over constructing highly ordered network architectures across multiple length scales could then be employed to integrate those building blocks into suitable forms for energy and biomedical purposes. 22–27 Inspired by this, we have proposed a facile strategy to fabricate a new class of all-small-molecule smart and antibacterial metallogels via the direct gelation of well-established small molecular synthons including aminoglycosides (AGs, a typical class of naturally occurring broad-spectrum antibiotics), 4,28–34 2,2′-bipyridine-4,4′-dicarboxaldehyde (BIPY), and metal ions.…”