Antibacterial activity of enrofloxacin loaded gelatin-sodium alginate composite nanogels against intracellular Staphylococcus aureus small colony variants

Abstract

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 (CaCl 2 ). 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.

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

“…The different values might be related to the difference in the nanomaterials’ physical statuses; the measured diameters using a Zeta sizer were in an aqueous status. As the free water and some hydrated water were exposed to evaporation, the enrofloxacin composite nanogels shrunk, resulting in a decrease in the particle sizes tested by SEM [ 14 ].…”

“…The COS–SA composite core-shell nanogels loaded with enrofloxacin were prepared according to previous reports [ 12 , 13 , 14 ]. Briefly, SA (100, 200, or 400 mg) and 25 mL ultrapure water were added together to form a suspension under a magnetic stirrer (HSC-19T, Qun’an Experimental Instrument Co., Ltd., Huzhou, China).…”

“…Each sample preparation was repeated three times. The EE and LC were defined as follows [ 14 ]: EE (%) = [(Weight of enrofloxacin added−weight of enrofloxacin in supernatant)/(Weight of enrofloxacin added)] × 100% LC (%) = [(Weight of enrofloxacin added−weight of enrofloxacin in supernatant)/(Weight of enrofloxacin composite nanogels)] × 100% …”

“…After the enrofloxacin nanogels were diluted 100 times, the Zeta ZX3600 (Malvern Instruments, Malvern, UK) was used to determine the mean particle size, ZP, and PDI [ 14 ].…”

Enhanced Cellular Delivery of Tildipirosin by Xanthan Gum–Gelatin Composite Nanogels

“…2,3 Therefore, increasing the concentration of antibiotics in infected cells is crucial, and a growing number of studies have proven that the use of novel carrier systems such as nanogels can enhance the antibiotics targeting efficiency for cell delivery. 4,5 It is interesting that novel macrolides, including tildipirosin, have drawn a lot of attention because of their quick penetration into infected tissues. 6 However, low intracellular drug concentrations and a brief intracellular residence time are the results of tildipirosin's unsatisfactory cellular absorption, resulting in a subpar intracellular delivery and the failure to cure intracellular bacterial infection.…”