In vitro and in vivo evaluation of a ciprofloxacin delivery system based on poly(DLLA-co-GA-co-CL) for treatment of chronic osteomyelitis

Abstract

Chronic osteomyelitis causes serious injury to patients. Antibiotic delivery systems based on poly(lactide-co-glycolide) (PLGA) have great potential for treatment of chronic osteomyelitis. However, PLGA has a glass-transition temperature that is higher than physiological temperatures, resulting in a lack of flexibility for implantation into the bone marrow cavity. As an alternative, poly(d, l-lactide-co-glycolide-co-ε-caprolactone) (PLGC) presents good flexibility due to the introduction of poly(ε-caprolactone) segments. To develop a new strategy for treatment of chronic osteomyelitis, a ciprofloxacin delivery system was prepared using PLGC as carriers, the antibacterial effects of which were evaluated both in vivo and in vitro. The in vitro release behavior showed that the average release reached 268.5 μg/days on day 33, with a cumulative release rate of 56.01%. A bacteriostatic ring, with a diameter of 26.83 ± 0.83 mm, was produced by ciprofloxacin against Staphylococcus aureus after 30 days of release via our ciprofloxacin-PLGC system. After 4 weeks of treatment in vivo, chronic-osteomyelitis-model rats had a bodyweight of 385.83 ± 17.23 g and a normal white-blood-cell count, as well as a lower number of bacterial colonies per gram of bone tissue of (10.6 ± 3.0) × 101 CFU/g. Furthermore, no inflammatory cells were observed via hematoxylin-and-eosin staining, and normal bone structure was observed via X-ray. Taken together, our findings indicate that our novel ciprofloxacin-PLGC system yielded noteworthy antibacterial effects both in vitro and in vivo, suggesting that it may be useful for treating patients with chronic osteomyelitis.

Efficacy Evaluation of Ciprofloxacin-Loaded Poly (Trimethylene Carbonate) Implants in the Treatment of Chronic Osteomyelitis

“…Furthermore, the release behaviour of PTMC implants was similar to that of poly (d, L-lactide-co-glycolide-co-ε-caprolactone) (PLGC) reported in our previous work (Liu et al, 2020). However, unlike PLGC, there is no second "burst release" caused by autocatalytic degradation of the acidic degradation products was observed for PTMC implants, resulting in much more stability of the PTMC implants and much more controllable to the release of ciprofloxacin HCL.…”

Formulation development, in vivo bioequivalence and pediatric PBPK modeling studies of taste-masked ciprofloxacin chewable tablets

“…Thermal analysis of the components of drug resin complex like a pure drug, Kyron T-134, physical mixture, and DRC was carried out on a Discovery DSC 250 instrument (TA instruments, New Castle, USA). The thermograms were recorded in the temperature range of 40–360 °C for each sample (4–10 mg) in a closed pan 16 .…”

Current research progress of local drug delivery systems based on biodegradable polymers in treating chronic osteomyelitis

“…The introduction of PCL structure into the PLGA chain endows better flexibility to the resulting copolymer poly(d, l-lactide-co-glycolide-co-ε-caprolactone) (PLGC). PLGC-based delivery systems loaded with ciprofloxacin are capable of maintaining sustained release of antibiotics for up to 30 days with sufficient concentrations to sustain long-term antimicrobial activity ( Liu and Bai, 2020 ). In a rat model of chronic osteomyelitis, the significant antibacterial effect of the PLGC/ciprofloxacin system was confirmed by the returned normal structure of proximal and middle tibiae ( Figure 6 ), indicating that the PLGC-based local antibiotic delivery system is a suitable candidate for treating chronic osteomyelitis.…”