Sustained Intra-Articular Release and Biocompatibility of Tacrolimus (FK506) Loaded Monospheres Composed of [PDLA-PEG1000]-b-[PLLA] Multi-Block Copolymers in Healthy Horse Joints.

There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained release of tacrolimus (FK506) from monospheres composed of [PDLA-PEG1000]-b-PLLA multiblock copolymers were investigated. Unloaded and tacrolimus-loaded (18.4 mg tacrolimus/joint) monospheres were injected into the joints of six healthy horses, with saline and hyaluronic acid (HA) in the contralateral joints as controls. Blood and synovial fluid were analysed for the tacrolimus concentration and biomarkers for inflammation and cartilage metabolism. After an initial burst release, sustained intra-articular tacrolimus concentrations (>20 ng/mL) were observed during the 42 days follow-up. Whole-blood tacrolimus levels were below the detectable level (<0.5 ng/mL). A transient inflammatory reaction was observed for all substances, evidenced by increases of the synovial fluid white blood cell count and total protein. Prostaglandin and glycosaminoglycan release were increased in joints injected with unloaded monospheres, which was mitigated by tacrolimus. Both tacrolimus-loaded monospheres and HA transiently increased the concentration of collagen II cleavage products (C2C). A histologic evaluation of the joints at the endpoint showed no pathological changes in any of the conditions. Together, these results indicate the good biocompatibility of intra-articular applied tacrolimus-loaded monospheres combined with prolonged local drug release while minimising the risk of systemic side effects. Further evaluation in a clinical setting is needed to determine if tacrolimus-loaded monospheres can be beneficial in the treatment of inflammatory joint diseases in humans and animals.

Sustained intra-articular release of celecoxib in an equine repeated LPS synovitis model.

Synovial inflammation is an important characteristic of arthritic disorders like osteoarthritis and rheumatoid arthritis. Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib are among the most widely prescribed drugs to manage these debilitating diseases. Intra-articular delivery in biodegradable in situ forming hydrogels overcomes adverse systemic effects and prolongs drug retention in the joint. In this study two formulations of celecoxib (40 mg/g and 120 mg/g) in a propyl-capped PCLA-PEG-PCLA triblock copolymer were sequentially evaluated in a multiple LPS challenge equine synovitis model. Intra-articular release and systemic exposure to celecoxib and local changes at joint level were evaluated longitudinally. A single intra-articular injection of the high dose (HCLB)-gel or low dose (LCLB)-gel showed a sustained and controlled intra-articular release in both inflamed and healthy joints together with very low systemic exposure. Synovitis and lameness were moderate respectively very mild in this model due to the low concentration LPS (0.25 ng/joint). Both celecoxib formulations had a mild, transient effect on inflammatory and structural synovial fluid biomarkers but these returned to baseline within one week of administration. The HCLB-gel showed a significant inhibition in peak white blood cell concentration at 8 h after LPS induction. Elevated levels of celecoxib were observed in the joint for up to 30 days but no overall anti-inflammatory effects could be observed, which was thought to be due to the moderate synovitis. As there were no long-term adverse effects, sustained intra-articular release of celecoxib from in situ forming hydrogels should be evaluated further for its effects on longer-term relief of inflammatory joint pain in humans and animals.

Laparoscopic ovariectomy in mares using a polyamide tie-rap.

OBJECTIVE: To describe use of a polyamide tie-rap to ligate the mesovarium during standing laparoscopic ovariectomy in mares. STUDY DESIGN: Prospective study. ANIMALS: Ten mares. METHODS: Bilateral ovariectomy was performed in 10 mares. Standing laparoscopic ovariectomy was performed using 3 portals in the paralumbar fossa. A commercial polyamide tie-rap was prepared as a loop and marked with 4 colored lines close to the buckle, to enable us to check whether the loop was tightened securely. The ovary was grasped with forceps and after the mesovarium was minimally transected cranially and caudally, the loop of the tie-rap was inserted in the abdomen and placed around the mesovarium. It was firmly tightened, until at least 3 of the 4 marks were visible, then the end of the tie-rap was cut. The ovary was transected and removed through an enlarged 3rd portal. The contralateral ovary was removed similarly through the opposite paralumbar fossa. Repeat laparoscopy was performed in 8 mares, 2, 3, 4, and 12 weeks later. RESULTS: None of the mares had postoperative discomfort. On repeat laparoscopy, there was complete encapsulation of the stump and tie-rap after 3-4 weeks. In 2 mares, an adhesion between the left stump and the mesentery of the descending colon was observed. CONCLUSION: Ligation of the mesovarium can be easily and safely performed using a polyamide tie-rap during standing laparoscopic ovariectomy in mares. CLINICAL RELEVANCE: Standing laparoscopic ovariectomy using a polyamide tie-rap is a safe, technically easy and reliable surgical procedure in the mare.

Surgical correction of ear curling caused by scar tissue formation in a horse.

An 18-month-old Belgian Warmblood mare was evaluated because it had injured the outer convex aspect of the left auricle. Second intention healing of the wound area caused tissue contracture, which resulted in the tip of the ear curling backward. By use of a technique involving undermining of the skin and a flap of granulation tissue on the medial aspect of the wound area and multiple incisions of the auricular cartilage, the curling was relieved and the ear regained a more normal shape. A skin graft was applied to cover the existing wound defect in an attempt to accelerate wound healing; thermoplastic material was contoured to fit the inner concave surface of the ear for immobilization and fixation of the ear in its final shape after surgery. Thirty days after surgery, the graft had healed completely and the ear had a normal conformation. The successful outcome of this treatment suggests that correction of an ear deformity secondary to scar tissue formation by use of an adapted surgical technique and appropriate materials can be achieved with good cosmetic results in horses.