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Background: Biofilms, such as those from Staphylococcus epidermidis , are generally insensitive to traditional antimicrobial agents, making it difficult to inhibit their formation. Although quercetin has excellent antibiofilm effects, its clinical applications are limited by the lack of sustained and targeted release at the site of S. epidermidis infection., Objectives: Polyethylene glycol-quercetin nanoparticles (PQ-NPs)-loaded gelatin-N,O-carboxymethyl chitosan (N,O-CMCS) composite nanogels were prepared and assessed for the on-demand release potential for reducing S. epidermidis biofilm formation., Methods: The formation mechanism, physicochemical characterization, and antibiofilm activity of PQ-nanogels against S. epidermidis were studied., Results: Physicochemical characterization confirmed that PQ-nanogels had been prepared by the electrostatic interactions between gelatin and N,O-CMCS with sodium tripolyphosphate. The PQ-nanogels exhibited obvious pH and gelatinase-responsive to achieve on-demand release in the micro-environment (pH 5.5 and gelatinase) of S. epidermidis . In addition, PQ-nanogels had excellent antibiofilm activity, and the potential antibiofilm mechanism may enhance its antibiofilm activity by reducing its relative biofilm formation, surface hydrophobicity, exopolysaccharides production, and eDNA production., Conclusions: This study will guide the development of the dual responsiveness (pH and gelatinase) of nanogels to achieve on-demand release for reducing S. epidermidis biofilm formation., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

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., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The stomach acid degradation, mucus clearance and intestinal epithelial impermeability severely limit the oral delivery of polypeptide drugs. To simultaneously address the three major barriers, novel self-assembled core-shell nanosystems (CA-NPs) were designed. The fabricated shell of citric acid cross-linked carboxymethyl cellulose (CA-CMC) wrapped on core nanoparticles (HA-NPs) maintained the integrity of CA-NPs in the stomach. When CA-NPs passed through the stomach, the CA-CMC shell was gradually degraded to release the core HA-NPs in the intestine. HA-NPs with numerous hydrophilic groups and mannose side chains rapidly penetrated through the mucus layer and efficiently transcellular transported via the glucose transporter (GLUT)-mediated and paracellular transport through reversible opening of tight junctions (TJs) by CA-CMC. The oral bioavailability and therapeutic effects of CA-NPs-loaded polypeptide colistin against Escherichia coli (E. coli) bacteremia in mice were significantly increased compared with the native colistin, respectively. Good safety was observed following oral daily delivery for 14 consecutive days. Thus, CA-NPs may offer a promising strategy for the oral delivery of polypeptide drugs., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest in this work., (Copyright © 2022. Published by Elsevier B.V.)

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., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Korean Society of Veterinary Science.)

Due to the poor solubility and permeability of rifaximin (RFX), it is not effective against intracellular pathogens although it shows strong activity against most bacteria. To develop an effective mucoadhesive drug delivery system with a targeted release in bacterial infection site, RFX-loaded chitosan (CS)/carboxymethyl-chitosan (CMCS) nanogel was designed and systematically evaluated. FTIR, DSC, and XRD demonstrated that the nanogel was formed by interactions between the positively charged NH 3 + on CS and CMCS, and the negatively charged COO on CMCS. RFX was encapsulated into the optimized nanogel in amorphous form. The nanogel was a uniform spherical shape with a mean diameter of 171.07 nm. It had excellent sustained release, strong mucin binding ability, and pH-responsive properties of quicker swelling and release at acidic pH. It showed low hemolytic ratio and high antioxidant activity. The present investigation indicated that the CS-nanogel could be potentially used as a promising bacterial responsiveness drug delivery system., (Copyright © 2020 Elsevier Ltd. All rights reserved.)