Evaluation of the antibacterial activity of tilmicosin-SLN against <em>Streptococcus agalactiae</em>: in vitro and in vivo studies

Abstract

BackgroundStreptococcus and Staphylococcus are the major contagious organisms causing dairy cow mastitis. Our previous studies have demonstrated that solid lipid nanoparticles (SLNs) can effectively enhance the antimicrobial activity of tilmicosin against Staphylococcus. This study aimed to evaluate the antibacterial efficacy of tilmicosin-loaded SLN (Til-SLN) against Streptococcus agalactiae.MethodsTil-SLN was prepared using a hot homogenization and ultrasonication method as described previously. Til-SLN was labeled with rhodamine B for nanoparticle tracking. In vitro antibacterial experiments were carried out by broth dilution technique. Pharmacokinetics of the drug and distribution of the nanoparticles in mammary gland were studied after subcutaneous injection in Kunming mice. The therapeutic study was conducted in a mouse mastitis model infected with S. agalactiae.ResultsThe results showed that the diameter, polydispersity index, zeta potential, encapsulation efficiency, and loading capacity of the nanoparticles were not significantly affected by fluorescence labeling. Til-SLN showed a sustained and enhanced antibacterial activity in vitro. Til-SLN maintained a sustained drug concentration above 17 µg/g for at least 6 days in the mammary gland, as compared with only 3 days for the same amount of tilmicosin phosphate solution. The mean residence time and elimination half-life (T1/2) of Til-SLN were much longer than those of tilmicosin phosphate solution. Most of the nanoparticles remained at the injection site and a few were transferred to the mammary glands, indicating that the drug was slowly released at the injection site and then distributed to the mammary glands. SLN significantly enhanced the therapeutic efficacy of tilmicosin as determined by lower colony forming unit counts.ConclusionThese results demonstrate that SLN could effectively enhance the antibacterial activity of tilmicosin against Streptococcus.

Enhanced Treatment Effects of Tilmicosin Against Staphylococcus aureus Cow Mastitis by Self-Assembly Sodium Alginate-Chitosan Nanogel

“…Our result agreed with the previous research. Tilmicosin HSO-SLNs obviously improved the treatment efficacy of tilmicosin in a mouse model of mastitis as determined by lowering the colony-forming unit counts [49]. One of the reasons why the TIL-SLNs and nanogel had higher in vivo antibacterial activity than the commercial tilmicosin injection might be because the liquid environment of a cow mammary was beneficial to the uniform distribution of TIL-SLNs and TIL-nanogel.…”

Advances in therapeutic and managemental approaches of bovine mastitis: a comprehensive review

“…The antibiotics that act by inhibiting protein synthesis exhibited significant synergistic effect when used along with silver nanoparticles (Kazemi et al 2014 ). The anti-bacterial activity of antibiotics like tilmicosin and amoxicillin can be enhanced by nanoformulation (Yang et al 2009 ; Zhu et al 2018 ). The solid lipid nanoparticles of tilmicosin exhibited prolonged and enhanced anti-bacterial activity against S. aureus and S. agalactiae (Zhu et al 2018 ).…”

“…The anti-bacterial activity of antibiotics like tilmicosin and amoxicillin can be enhanced by nanoformulation (Yang et al 2009 ; Zhu et al 2018 ). The solid lipid nanoparticles of tilmicosin exhibited prolonged and enhanced anti-bacterial activity against S. aureus and S. agalactiae (Zhu et al 2018 ). Amoxicillin nanoparticles enhanced the post-antibiotic effect and reduced the dosing interval when used against pathogenic bacteria causing bovine mastitis (Yang et al 2009 ).…”

“…Nanoparticle technology is another area that is currently developing as a delivery technique for antimicrobial agents and other drugs (Gomes & Henriques, 2016) (Zhu et al 2018). Amoxicillin nanoparticles enhanced the post-antibiotic effect and reduced the dosing interval when used against pathogenic bacteria causing bovine mastitis (Yang et al 2009).…”

Pharmacokinetics and bioavailability of solid dispersion formulation of tilmicosin in pigs

“…A comparison of TMS enteric granules and premix in pigs indicated the relative bioavailability of TMS enteric granules to premix was 114.97% (Xiong, Zhu, Zhao, et al., 2019). The use of TMS solid lipid nanoparticles after subcutaneous injection in Kunming mice demonstrated a relative bioavailability compared with TMS phosphate of 600% (Zhu et al., 2018). Although the solid lipid nanoparticles of TMS had the highest bioavailability, its widespread application has been hampered by the high cost of production.…”