Purpose Curcumin has shown a variety of biological activity for various human diseases including cancer in preclinical setting. Its poor oral bioavailability poses significant pharmacological barriers to its clinical application. Here, we established a practical nano-emulsion curcumin (NEC) containing up to 20% curcumin (w/w) and conducted the pharmacokinetics of curcuminoids and curcumin metabolites in mice. Methods This high loading NEC was formulated based on the high solubility of curcumin in polyethylene glycols (PEGs) and the synergistic enhancement of curcumin absorption by PEGs and Cremophor EL. The pharmacokinetics of curcuminoids and curcumin metabolites was characterized in mice using a LC–MS/MS method, and the pharmacokinetic parameters were determined using WinNonlin computer software. Results A tenfold increase in the AUC0→24h and more than 40-fold increase in the Cmax in mice were observed after an oral dose of NEC compared with suspension curcumin in 1% methylcellulose. The plasma pharmacokinetics of its two natural congeners, demethoxycurcumin and bisdemethoxycurcumin, and three metabolites, tetrahydrocurcumin (THC), curcumin-O-glucuronide, and curcumin-O-sulfate, was characterized for the first time in mice after an oral dose of NEC. Conclusion This oral absorption enhanced NEC may provide a practical formulation to conduct the correlative study of the PK of curcuminoids and their pharmacodynamics, e.g., hypomethylation activity in vivo.

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Objective: The aim was to investigate the clinical relevance of preoperative caudal adjacent segment degeneration (ASD) in patients undergoing isolated L4-5 fusion to determine a threshold of degeneration at which a primary L4-S1 fusion would be warranted.Summary of Background Data: Increased motion and biomechanical forces across the adjacent caudal segment in isolated L4-L5 fusion leads to concerns regarding the increased incidence of revision surgery because of the development of ASD.Methods: Patients who underwent isolated L4-L5 fusion between 2014 and 2019 were reviewed. Pfirrmann grading and the disc heights of the caudal level relative to the rostral level were used to quantify preoperative adjacent degenerative disc disease. To assess the influence of preoperative caudal degenerative disc disease, preoperative disc height ratios (DHRs) were compared for patients who reported minimal, moderate, and severe Oswestry disability index (ODI) sores on postoperative assessment. For each patient-reported outcome measure (PROM), adjacent DDD was compared for those who did and did not meet MCID. An area under curve analysis was used to identify a threshold of degeneration impacting outcomes from the preoperative DHR.Results: A total of 123 patients were studied with an average follow-up of 2.11 years. All patients demonstrated a significant improvement in all PROMs after surgery. When categorizing patients based on the severity of postoperative ODI scores, there were no preoperative differences in the L5-S1 Pfirrmann grading or DHRs. There was a significant association between greater preoperative anterior DHR and an increased number patients who met MCID for visual analog scale back. There were no radiographic differences in preoperative L5-S1 Pfirrmann grade or DHR for ODI, visual analog scale leg, MCS-12, or PCS-12. area under curve analysis was not able to identify a preoperative DHR threshold that reflected worse MCID for any PROM. Conclusion:No preoperative radiographic indicators of caudal ASD were predictive of worse clinical outcomes after isolated L4-5 fusion.