On-demand release of enrofloxacin-loaded chitosan oligosaccharide-oxidized hyaluronic acid composite nanogels for infected wound healing.

In this study, enrofloxacin (ENR) was encapsulated by oxidized hyaluronic acid (OHA) containing aldehyde groups and chitosan oligosaccharide (COS) containing amino groups through Schiff's base reaction to achieve on-demand release in the micro-environment (pH 5.5 and HAase) of bacterial-infected wounds (Escherichia coli and Staphylococcus aureus). The formation mechanism, physicochemical characterization, responsive release performance, in vitro and in vivo antimicrobial activities, and in vivo regeneration in full-thickness wounds in a bacterial-infected mouse model of the ENR nanogels were systematically studied. According to the single-factor experiment and Design-Expert software, the optimized formula was 3.8 mg/ml COS, 0.5 mg/ml OHA, and 0.3 mg/ml ENR, respectively. The mean particle diameter, polydispersity index, zeta potential, loading capacity, and encapsulation efficiency were 35.6 ± 1.7 nm, -6.7 ± 0.5 mV, 0.25 ± 0.02, 30.4 % ± 1.3 %, and 76.3 % ± 2.6 %, respectively. The appearance, optical microscopy images, SEM, TEM, PXRD, and FTIR showed that the ENR nanogels were successfully prepared. The ENR nanogels exhibited obvious pH and HAase-responsiveness by swelling ratios and in vitro release and had stronger antibacterial activity with time-dependent and concentration-dependent effects, as well as accelerating infected wound healing. In vitro and in vivo biosafety studies suggested the great promise of ENR nanogels as biocompatible wound dressings for infected wounds.

Antibacterial activity of a novel glycyrrhizic acid-loaded chitosan composite nanogel in vitro against Staphylococcus aureus small colony variants.

Background This study aimed to improve the sustained and controlled release of glycyrrhizic acid to the infected site of Staphylococcus aureus small colony variants (SCVs). Methods The glycyrrhizic acid-loaded chitosan composite nanogel was prepared by inclusion action, Schiff's base formation, and electrostatic action. Furthermore, the formulation screening, characteristics, in vitro release, and antibacterial activity of the glycyrrhizic acid composite nanogel were explored. Results The final optimal formula comprised 10 mg/mL (chitosan) and 50 µL (glutaraldehyde). The loading capacity, encapsulation efficiency, mean size, polydispersity index, and zeta potential were 8.8%±1.6%, 92.1%±2.8%, 478.3±2.8 nm, 0.37±0.10, and 25.3±3.6 mv, respectively. Scanning electron microscope images showed a spherical shape with a relatively uniform distribution. The in vitro release study showed that glycyrrhizic acid composite nanogel exhibited a biphasic pattern with a sustained release of 52.1%±2.0% at 48 h in the pH 5.5 PBS. The minimum inhibitory and minimum biofilm inhibitory concentrations of glycyrrhizic acid composite nanogel against SCVs were 0.625 µg/mL. The time-killing curves and live/dead bacterial staining showed that glycyrrhizic acid composite nanogel had a stronger curative effect against SCVs strain with concentration-dependent. Conclusion This study provides promising glycyrrhizic acid composite nanogel to improve the treatment of SCV infection.

Intelligent-Responsive Enrofloxacin-Loaded Chitosan Oligosaccharide-Sodium Alginate Composite Core-Shell Nanogels for On-Demand Release in the Intestine.

Enrofloxacin has a poor palatability and causes strong gastric irritation; the oral formulation of enrofloxacin is unavailable, which limits the treatment of Escherichia coli (E. coli) infections via oral administration. To overcome the difficulty in treating intestinal E. coli infections, an oral intelligent-responsive chitosan-oligosaccharide (COS)-sodium alginate (SA) composite core-shell nanogel loaded with enrofloxacin was explored. The formulation screening, characteristics, pH-responsive performance in gastric juice and the intestinal tract, antibacterial effects, therapeutic effects, and biosafety level of the enrofloxacin composite nanogels were investigated. The optimized concentrations of COS, SA, CaCl2, and enrofloxacin were 8, 8, 0.2, and 5 mg/mL, respectively. The encapsulation efficiency, size, loading capacity, zeta potential, and polydispersity index of the optimized formulation were 72.4 ± 0.8%, 143.5 ± 2.6 nm, 26.6 ± 0.5%, -37.5 ± 1.5 mV, and 0.12 ± 0.07, respectively. Scanning electron microscopy images revealed that enrofloxacin-loaded nanogels were incorporated into the nano-sized cross-linked networks. Fourier transform infrared spectroscopy showed that the nanogels were prepared by the electrostatic interaction of the differently charged groups (positive amino groups (-NH3+) of COS and the negative phenolic hydroxyl groups (-COO-) of SA). In vitro, pH-responsive release performances revealed effective pH-responsive performances, which can help facilitate targeted "on-demand" release at the target site and ensure that the enrofloxacin has an ideal stability in the stomach and a responsive release in the intestinal tract. The antibacterial activity study demonstrated that more effective bactericidal activity against E. coli could have a better treatment effect than the enrofloxacin solution. Furthermore, the enrofloxacin composite nanogels had great biocompatibility. Thus, the enrofloxacin composite core-shell nanogels might be an oral intelligent-responsive preparation to overcome the difficulty in treating intestinal bacterial infections.

Antibacterial activity of florfenicol composite nanogels against Staphylococcus aureus small colony variants.

BACKGROUND: Florfenicol might be ineffective for treating Staphylococcus aureus small colony variants (SCVs) mastitis. OBJECTIVES: In this study, florfenicol-loaded chitosan (CS)-sodium tripolyphosphate (TPP) composite nanogels were prepared to allow targeted delivery to SCV infected sites. METHODS: The formulation screening, the characteristics, in vitro release, antibacterial activity, therapeutic efficacy, and biosafety of the florfenicol composite nanogels were studied. RESULTS: The optimized formulation was obtained when the CS and TPP were 10 and 5 mg/mL, respectively. The encapsulation efficiency, loading capacity, size, polydispersity index, and zeta potential of the optimized florfenicol composite nanogels were 87.3% ± 2.7%, 5.8% ± 1.4%, 280.3 ± 1.5 nm, 0.15 ± 0.03, and 36.3 ± 1.4 mv, respectively. Optical and scanning electron microscopy showed that spherical particles with a relatively uniform distribution and drugs might be incorporated in cross-linked polymeric networks. The in vitro release study showed that the florfenicol composite nanogels exhibited a biphasic pattern with the sustained release of 72.2% ± 1.8% at 48 h in pH 5.5 phosphate-buffered saline. The minimal inhibitory concentrations of commercial florfenicol solution and florfenicol composite nanogels against SCVs were 1 and 0.25 µg/mL, respectively. The time-killing curves and live-dead bacterial staining showed that the florfenicol composite nanogels were concentration-dependent. Furthermore, the florfenicol composite nanogels displayed good therapeutic efficacy against SCVs mastitis. Biological safety studies showed that the florfenicol composite nanogels might be a biocompatible preparation because of their non-toxic effects on the renal tissue and liver. CONCLUSIONS: Florfenicol composite nanogels might improve the treatment of SCV infections.