Treatment of contaminated radial fracture in Sprague-Dawley rats by application of a degradable polymer releasing gentamicin

Abstract

Fracture-related infections remain a leading cause of morbidity and mortality. We aimed to establish a simple contaminated radial osteotomy model to assess the efficacy of a biodegradable polymer poly(sebacic-co-ricinoleic acid) [p(SA-RA)] containing 20% w/w gentamicin. A unilateral transverse osteotomy was induced in Sprague-Dawley (SD) rats, followed by application of Staphylococcus aureus suspension over the fracture. After successfully establishing the contaminated open fracture model, we treated the rats either systemically (intraperitoneal cefuroxime), locally with p(SA-RA) containing gentamicin, or both. Control groups included non-contaminated group and contaminated groups that were either untreated or treated with the polymer alone. After 4 weeks, the bones were subjected to micro-CT scanning and microbiological and histopathology evaluations. Micro-CT analysis revealed similar changes in the group subjected to both local and systemic treatment as in the non-contaminated control group. Lack of detectable bacterial growth was noted in most animals of the group subjected to both local and systemic treatment, and all samples were negative for S. aureus . Histopathological evaluation revealed that all treatment modalities containing antibiotics were highly effective in reducing infection and promoting callus repair, resulting in early bone healing. While p(SA-RA) containing gentamicin treatment showed better results than cefuroxime, the combination of local and systemic treatment displayed the highest therapeutic potential in this model.

Synthesis of Aliphatic Polyanhydrides with Controllable and Reproducible Molecular Weight

“…Polyanhydrides have been widely explored as biodegradable polymers for the last four decades [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. In 1909, Bucher and Slade first synthesized polyanhydrides upon heating isophthalic acid and terephthalic acid in presence of acetic anhydride [ 1 ].…”

“…Polyanhydrides in the form of slabs, films, rods, microspheres and nanospheres, have been used as therapeutic delivery devices [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Gliadel wafers are in clinical use for the delivery of carmustine (bis-chloroethylnitrosourea, BCNU) for the treatment of brain cancer.…”

“…This device allowed the localized and controlled delivery of BCNU over several weeks that provides high drug concentration in the tumor site with little systemic distribution which reduces BCNU side effects [ 6 , 7 ]. Local delivery antibiotic implant was constructed with fatty acid based polyanhydride for the treatment of osteomyelitis [ 10 , 11 ]. The implant was used to deliver gentamicin sulfate.…”

Poly(ester-anhydrides) Derived from Esters of Hydroxy Acid and Cyclic Anhydrides

“…The safety of polyester anhydrides, particularly poly­(sebacic acid-ricinoleic acid) 30:70, is reported . The polymers degrade into their starting materials that are eliminated from the site of injection and the body. , …”

“…The safety of polyester anhydrides, particularly poly(sebacic acid-ricinoleic acid) 30:70, is reported. 20 The polymers degrade into their starting materials that are eliminated from the site of injection and the body. 21,22 On the other hand, there is a growing demand for injectable systems using viscous low melting polymers that facilitate new potential uses for the polyanhydrides.…”