Antibiotic loaded solid lipid nanoparticles target bacteria in a pyogenic spondylitis rat model.

Preclinical study involving in vitro characterization and an in vivo rat model of pyogenic spondylitis.

“Furthermore, antibacterial activity, bacterial-targeting capability, and therapeutic efficacy were evaluated using Enterococcus faecalis-infected mesenchymal stem cells and a rat model of pyogenic spondylitis.”

Male Sprague-Dawley rats and Enterococcus faecalis-infected mesenchymal stem cells.

“Thirty male Sprague-Dawley rats were commercially obtained from Raonbio Inc. (Yongin, Republic of Korea).”

Thirty male Sprague-Dawley rats divided into four groups (Normal n=3, infection-only n=4, AMP n=4, LL-37@AMP-SLNs n=4).

“Thirty male Sprague-Dawley rats were divided into a without-infection group (Normal, n = 3), an infection-only group (infection-only, n = 4), an infection + AMP group (AMP, n = 4), and an infection + LL-37@AMP-SLNs group (LL-37@AMP-SLNs, n = 4).”

Seven days of treatment following a seven-day infection establishment period.

“Seven days after transplantation, 20 mg/mL of AMP and 10 mg/mL of LL-37@AMP-SLNs were injected in the AMP group and the LL-37@AMP-SLNs group, respectively, via tail vein injection for seven consecutive days.”

LL-37@AMP-SLNs exhibited enhanced antibacterial activity and bacterial-targeting capability compared to unmodified SLNs and AMP-SLNs in vitro.

“The LL-37@AMP-SLNs exhibited sustained AMP release over four days and demonstrated enhanced antibacterial activity and bacterial-targeting capability compared with unmodified SLNs and AMP-SLNs.”

In the rat model, LL-37@AMP-SLNs treatment significantly reduced bacterial burden and improved therapeutic outcomes compared to free AMP treatment.

“Moreover, the LL-37@AMP-SLNs treatment led to significantly enhanced antibacterial effects.”

Histological analysis showed decreased gram-positive bacteria levels in the LL-37@AMP-SLNs group compared to infection-only and AMP groups.

“Fourteen days after Pyogenic spondylitis, the number of gram-positive bacteria in the LL-37@AMP-SLNs group was decreased compared to those in the infection-only and AMP groups (Fig. 5B, infection-only: 59.26% ± 3.17, AMP: 21.78% ± 2.16, and LL-37@AMP-SLNs: 6.24% ± 1.57, ***p < 0.001).”

Loading efficiency, surface density of LL-37, serum stability, biodistribution, pharmacokinetics, and in vivo targeting efficiency were not evaluated.

“The loading efficiency and surface density of LL-37 on AMP-SLNs were not quantitatively determined, and the serum stability, biodistribution, pharmacokinetics, and in vivo targeting efficiency of the nanoparticles were not directly evaluated.”