Are Anidulafungin or Voriconazole Released from Polymethylmethacrylate In Vitro?

Abstract

Background Depot delivery of antimicrobial agents is used for treatment and prevention of bacterial orthopaedic infections; there is little information regarding newer antifungal agents and their potential use in polymethylmethacrylate (PMMA) depot delivery. Questions/purposes We determined the percent of anidulafungin or voriconazole present after polymerization in PMMA beads loaded with anidulafungin or voriconazole, and we assessed elution of anidulafungin or voriconazole from beads loaded with anidulafungin or voriconazole. Materials and Methods Beads containing 7.5% anidulafungin or voriconazole were pulverized and incubated in Kreb's ringer buffer for 48 hours; the buffer was assayed for anidulafungin or voriconazole concentration. The in vitro release of anidulafungin and voriconazole from PMMA beads loaded with 7.5% anidulafungin or voriconazole was determined in triplicate in a continuous flow chamber.Results 0.7% of anidulafungin and 5.6% of voriconazole loaded in the beads were detected after polymerization. No anidulafungin was detected in the elution studies. The mean peak voriconazole concentration in the elution studies was 0.9 lg/mL. Conclusions Anidulafungin may not be suitable for depot delivery in PMMA.

Voriconazole Is Delivered From Antifungal-Loaded Bone Cement

“…Of the published studies that report release data on antifungals [6,9,[14][15][16], two report voriconazole release data [6,14] ( Table 1). Both studies report release of voriconazole but had important methodological and formulation differences from our study.…”

“…It is not known if this difference in delivery efficiency will have a meaningful difference in clinical efficacy. Rouse et al [14] report that small amounts of voriconazole are released from ALBC made with 98% pure voriconazole, presumably containing no b-cyclodextrin. This is a low-dose formulation that has low porosity and would not be expected to have the high release (63%) seen in our study.…”

“…More studies are needed to determine voriconazole toxicity to local tissues at the high levels delivered by local depot. Rouse et al [14] did not determine bioactivity of the delivered voriconazole; Grimsrud et al [6] tested bioactivity at 1 and 2 weeks. This report confirms the activity of delivered voriconazole at all collection time points, verifying that active voriconazole is delivered from the cement.…”

“…They used 800 mg/batch (approximately 30 vol%) in their ALBC formulation, but cumulative mass of voriconazole recovered in infinite sink conditions was not performed. Rousse et al [14] reported release from ALBC made with 7.5 wt% anidulafungin or voriconazole. The voriconazole used in the study by Rousse et al was reported as 98% pure.…”

Elution of High Dose Amphotericin B Deoxycholate From Polymethylmethacrylate

“…The concentration of amphotericin B was measured from the buffer. Second, three amphotericin beads were placed in a previously-described in vitro elution chamber [6][7][8]15].Briefly, amphotericin B was added to Surgical Simplex P radiopaque bone cement (Stryker Orthopedics, Mahwah, NJ, USA) and methyl methacrylate liquid. Beads containing 7.5% (weight/weight) amphotericin B were prepared by mixing 1.5 g amphotericin B deoxycholate powder (X-Gen Pharmaceuticals Inc., Big Flats, NY) with 20 g of cement powder.…”