Purpose: Fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] is a cytotoxic retinoid that suffers from a wide interpatient variation in bioavailability when delivered orally in a corn oil capsule. The poor bioavailability of the capsule formulation may have limited responses in clinical trials, and the large capsules are not suitable for young children. To support the hypothesis that a novel organized lipid matrix, LYM-X-SORB, can increase the oral bioavailability of fenretinide, fenretinide in LYM-X-SORB matrix and in a powderized LYM-X-SORB formulation was delivered to mice. Experimental Design: Fenretinide was delivered orally to mice as the contents of the corn oil capsule, in LYM-X-SORB matrix (4-HPR/LYM-X-SORB matrix) or in a LYM-X-SORB matrix powderized with sugar and flour (4-HPR/LYM-X-SORB oral powder). Levels of 4-HPR, and its principal metabolite, N-(4-methoxyphenyl)retinamide, were assayed in plasma and tissues. Results: In a dose-responsive manner, from 120 to 360 mg/kg/d, delivery to mice of 4-HPR in LYM-X-SORB matrix, or as 4-HPR/LYM-X-SORB oral powder, increased 4-HPR plasma levels up to 4-fold (P < 0.01) and increased tissue levels up to 7-fold (P < 0.01) compared with similar doses of 4-HPR delivered using capsule contents. Metabolite [N-(4-methoxyphenyl)retinamide] levels mirrored 4-HPR levels. Two human neuroblastoma murine xenograft models showed increased survival (P < 0.03), when treated with 4-HPR/LYM-X-SORB oral powder, confirming the bioactivity of the formulation. Conclusions: 4-HPR/LYM-X-SORB oral powder is a novel, oral drug delivery formulation, suitable for pediatric use, which warrants further development for the delivery of fenretinide in the treatment of cancer. A phase I clinical trial in pediatric neuroblastoma is in progress.

Metal transfer to femoral heads may result from impingement against the metallic acetabular shell following subluxation/dislocation, or when metallic debris enters the articulation zone. Such transfers roughen the head surface, increasing polyethylene wear in total hip replacements. Presently, we examined the surface roughness of retrieved femoral heads with metallic transfer. Profilometry revealed roughness averages in regions of metal transfer averaging 0.380 μm for CoCr and 0.294 μm for ZrO2 which were one order of magnitude higher than those from non-implanted controls. Scanning electron microscopy (SEM) revealed adherent transfers on these retrievals, with titanium presence confirmed by electron dispersive spectroscopy. Due to the concern for increased wear, metal transfer was induced on non-implanted heads, which were then articulated against flat polyethylene discs in multidirectional sliding wear tests. Increased polyethylene wear was associated with these specimens as compared to unaltered controls. SEM imaging provided visual evidence that the transfers remained adherent following the wear tests. Pre- and post-test roughness averages exceeded 1 μm for both the CoCr and ZrO2 heads. Overall, these results suggest that metal transfer increases the surface roughness of CoCr and ZrO2 femoral heads and that the transfers may remain adherent following articulation against polyethylene, leading to increased polyethylene wear.