1.Antibacterial activity of enrofloxacin loaded gelatin-sodium alginate composite nanogels against intracellular Staphylococcus aureus small colony variants
Wanhe LUO ; Jinhuan LIU ; Samah Attia ALGHARIB ; Wei CHEN
Journal of Veterinary Science 2022;23(3):e48-
Background:
The poor intracellular concentration of enrofloxacin might lead to treatment failure of cow mastitis caused by Staphylococcus aureus small colony variants (SASCVs).
Objectives:
In this study, enrofloxacin composite nanogels were developed to increase the intracellular therapeutic drug concentrations and enhance the efficacy of enrofloxacin against cow mastitis caused by intracellular SASCVs.
Methods:
Enrofloxacin composite nanogels were formulated by an electrostatic interaction between gelatin (positive charge) and sodium alginate (SA; negative charge) with the help of CaCl 2 (ionic crosslinkers) and optimized by a single factor test using the particle diameter, zeta potential (ZP), polydispersity index (PDI), loading capacity (LC), and encapsulation efficiency (EE) as indexes. The formation mechanism, structural characteristics, bioadhesion ability, cellular uptake, and the antibacterial activity of the enrofloxacin composite nanogels against intracellular SASCVs strain were studied systematically.
Results:
The optimized formulation was comprised of 10 mg/mL (gelatin), 5 mg/mL (SA), and 0.25 mg/mL (CaCl2). The size, LC, EE, PDI, and ZP of the optimized enrofloxacin composite nanogels were 323.2 ± 4.3 nm, 15.4% ± 0.2%, 69.6% ± 1.3%, 0.11 ± 0.02, and −34.4 ± 0.8 mV, respectively. Transmission electron microscopy showed that the enrofloxacin composite nanogels were spherical with a smooth surface and good particle size distributions. In addition, the enrofloxacin composite nanogels could enhance the bioadhesion capacity of enrofloxacin for the SASCVs strain by adhesive studies. The minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibitory concentration, and minimum biofilm eradication concentration were 2, 4, 4, and 8 μg/mL, respectively. The killing rate curve had a concentration-dependent bactericidal effect as increasing drug concentrations induced swifter and more radical killing effects.
Conclusions
This study provides a good tendency for developing enrofloxacin composite nanogels for treating cow mastitis caused by intracellular SASCVs and other intracellular bacterial infections.
2.Formulation of a rational dosage regimen of ceftiofur hydrochloride oily suspension by pharmacokineticpharmacodynamic (PK-PD) model for treatment of swine Streptococcus suis infection
Wanhe LUO ; Dehai WANG ; Hua QIN ; Dongmei CHEN ; Yuanhu PAN ; Wei QU ; Lingli HUANG ; Shuyu XIE
Journal of Veterinary Science 2021;22(6):e41-
Background:
Our previously prepared ceftiofur (CEF) hydrochloride oily suspension shows potential wide applications for controlling swine Streptococcus suis infections, while the irrational dose has not been formulated.
Objectives:
The rational dose regimens of CEF oily suspension against S. suis were systematically studied using a pharmacokinetic-pharmacodynamic model method.
Methods:
The healthy and infected pigs were intramuscularly administered CEF hydrochloride oily suspension at a single dose of 5 mg/kg, and then the plasma and pulmonary epithelial lining fluid (PELF) were collected at different times. The minimum inhibitory concentration (MIC), minimal bactericidal concentration, mutant prevention concentration (MPC), post-antibiotic effect (PAE), and time-killing curves were determined. Subsequently, the area under the curve by the MIC (AUC 0–24h /MIC) values of desfuroylceftiofur (DFC) in the PELF was obtained by integrating in vivo pharmacokinetic data of the infected pigs and ex vivo pharmacodynamic data using the sigmoid E max (Hill) equation. The dose was calculated based on the AUC 0–24h /MIC values for bacteriostatic action, bactericidal action, and bacterial elimination.
Results:
The peak concentration, the area under the concentration-time curve, and the time to peak for PELF's DFC were 24.76 ± 0.92 µg/mL, 811.99 ± 54.70 μg·h/mL, and 8.00 h in healthy pigs, and 33.04 ± 0.99 µg/mL, 735.85 ± 26.20 μg·h/mL, and 8.00 h in infected pigs, respectively. The MIC of PELF's DFC against S. suis strain was 0.25 µg/mL. There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves. The AUC 0–24h /MIC values of PELF's DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 6.54 h, 9.69 h, and 11.49 h, respectively. Thus, a dosage regimen of 1.94 mg/kg every 72 h could be sufficient to reach bactericidal activity.
Conclusions
A rational dosage regimen was recommended, and it could assist in increasing the treatment effectiveness of CEF hydrochloride oily suspension against S. suis infections.
3.Enhanced antibacterial activity of tilmicosin against Staphylococcus aureus small colony variants by chitosan oligosaccharide-sodium carboxymethyl cellulose composite nanogels
Wanhe LUO ; Jinhuan LIU ; Shanling ZHANG ; Wei SONG ; Samah Attia ALGHARIB ; Wei CHEN
Journal of Veterinary Science 2022;23(1):e1-
Background:
The poor bioadhesion capacity of tilmicosin resulting in treatment failure for Staphylococcus aureus small colony variants (SASCVs) mastitis.
Objectives:
This study aimed to increase the bioadhesion capacity of tilmicosin for the SASCVs strain and improve the antibacterial effect of tilmicosin against cow mastitis caused by the SASCVs strain.
Methods:
Tilmicosin-loaded chitosan oligosaccharide (COS)-sodium carboxymethyl cellulose (CMC) composite nanogels were formulated by an electrostatic interaction between COS (positive charge) and CMC (negative charge) using sodium tripolyphosphate (TPP) (ionic crosslinkers). The formation mechanism, structural characteristics, bioadhesion, and antibacterial activity of tilmicosin composite nanogels were studied systematically.
Results:
The optimized formulation was comprised of 50 mg/mL (COS), 32 mg/mL (CMC), and 0.25 mg/mL (TPP). The size, encapsulation efficiency, loading capacity, polydispersity index, and zeta potential of the optimized tilmicosin composite nanogels were 357.4 ± 2.6 nm, 65.4 ± 0.4%, 21.9 ± 0.4%, 0.11 ± 0.01, and -37.1 ± 0.4 mV, respectively; the sedimentation rate was one. Scanning electron microscopy showed that tilmicosin might be incorporated in nano-sized crosslinked polymeric networks. Moreover, adhesive studies suggested that tilmicosin composite nanogels could enhance the bioadhesion capacity of tilmicosin for the SASCVs strain. The inhibition zone of native tilmicosin, tilmicosin standard, and tilmicosin composite nanogels were 2.13 ± 0.07, 3.35 ± 0.11, and 1.46 ± 0.04 cm, respectively. The minimum inhibitory concentration of native tilmicosin, tilmicosin standard, and tilmicosin composite nanogels against the SASCVs strain were 2, 1, and 1 µg/mL, respectively. The in vitro time-killing curves showed that the tilmicosin composite nanogels increased the antibacterial activity against the SASCVs strain.
Conclusions
This study provides a potential strategy for developing tilmicosin composite nanogels to treat cow mastitis caused by the SASCVs strain.
4.Antibacterial activity of florfenicol composite nanogels against Staphylococcus aureus small colony variants
Jinhuan LIU ; Mujie JU ; Yifei WU ; Nannan LENG ; Samah Attia ALGHARIB ; Wanhe LUO
Journal of Veterinary Science 2022;23(5):e78-
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 concentrationdependent. 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.
5.Antibiofilm activity of polyethylene glycol-quercetin nanoparticlesloaded gelatin-N,O-carboxymethyl chitosan composite nanogels against Staphylococcus epidermidis
Wanhe LUO ; Yongtao JIANG ; Jinhuan LIU ; Beibei SUN ; Xiuge GAO ; Samah Attia ALGHARIB ; Dawei GUO ; Jie WEI ; Yurong WEI
Journal of Veterinary Science 2024;25(2):e30-
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,Ocarboxymethyl 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.
6.Pharmacokinetics/Pharmacodynamics models of veterinary antimicrobial agents
Wanhe LUO ; Dongmei CHEN ; Mengru WU ; Zhenxia LI ; Yanfei TAO ; Qianying LIU ; Yuanhu PAN ; Wei QU ; Zonghui YUAN ; Shuyu XIE
Journal of Veterinary Science 2019;20(5):e40-
Misuse and abuse of veterinary antimicrobial agents have led to an alarming increase in bacterial resistance, clinical treatment failure, and drug residues. To address these problems, consistent and appropriate dosage regimens for veterinary antimicrobial agents are needed. Pharmacokinetics/Pharmacodynamics (PK/PD) models have been widely used to establish rational dosage regimens for veterinary antimicrobial agents that can achieve effective prevention and treatment of bacterial diseases and avoid the development of bacterial resistance. This review introduces building methods for PK/PD models and describes current PK/PD research progress toward rational dosage regimens for veterinary antimicrobial agents. Finally, the challenges and prospects of PK/PD models in the design of dosage regimens for veterinary antimicrobial agents are reviewed. This review will help to increase awareness of PK/PD modeling among veterinarians and hopefully promote its development and future use.
Anti-Infective Agents
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Bacterial Infections
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Drug Residues
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Humans
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Treatment Failure
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Veterinarians
7.Basic concepts, recent advances, and future perspectives in the diagnosis of bovine mastitis
Samah Attia ALGHARIB ; Ali Sobhy DAWOOD ; Lingli HUANG ; Aizhen GUO ; Gang ZHAO ; Kaixiang ZHOU ; Chao LI ; Jinhuan LIU ; Xin GAO ; Wanhe LUO ; Shuyu XIE
Journal of Veterinary Science 2024;25(1):e18-
Mastitis is one of the most widespread infectious diseases that adversely affects the profitability of the dairy industry worldwide. Accurate diagnosis and identification of pathogens early to cull infected animals and minimize the spread of infection in herds is critical for improving treatment effects and dairy farm welfare. The major pathogens causing mastitis and pathogenesis are assessed first. The most recent and advanced strategies for detecting mastitis, including genomics and proteomics approaches, are then evaluated .Finally, the advantages and disadvantages of each technique, potential research directions, and future perspectives are reported. This review provides a theoretical basis to help veterinarians select the most sensitive, specific, and cost-effective approach for detecting bovine mastitis early.