Elution Profile of Caspofungin from Anti-fungal Loaded Bone Cement

Advancements in healthcare and the emergence of an aging population has led to an increase in the number of prosthetic joint procedures in the United States. According to Healthcare Cost and Utilization Project, 660,876 and 348,970 total hip and knee arthroplasties were performed in 2014[1].The percentage of total hip or knee procedures that are revised due to an infection is 1.23% and 1.21% respectively[3], [4]. Although the percent of infections may be small, an infection can have a tremendous burden on the patient and healthcare system. It is expected that prosthetic joint infections (PJIs) will cost the healthcare system an estimated $1.62 billion by 2020[5]. PJIs are often difficult to treat due to the formation of biofilm at the site of the infection. A large majority of PJIs are the result of a bacterial biofilm, but around 1% of PJIs are due to fungal infections[3]. The current method of treatment is to surgically remove all infected tissue at the site of infection through a process called debridement and then insert a medicated bone cement spacer[7], [10]–[12]. One such medication that is loaded into the bone cement is caspofungin, a member of the echinocandin class of compounds that inhibit the synthesis of 1,3-β-D-glucan which is a crucial element of the cell wall of the target fungi[13]–[15]. For the studies reported herein, the caspofungin-loaded bone cement samples were made at 5 dosage strengths according to standard operating room practices. The elution of the drug was analyzed using ultraviolet spectrophotometry. The elution profiles were analyzed for 19 days consecutively, during which the 70 mg, 1 g, and 5 g dosage groups showed a prolonged, sustained release of the caspofungin. The 70 mg and 1 g dosage cumulative mass release profiles were not statistically significant, but it is unlikely that the difference would not have a clinical significance especially in the treatment of a fungal biofilm infection. The determination of the elution profile for caspofungin from loaded-bone cement can provide clinicians with a basis for how the drug will release into the infected joint.