School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, United States.
Department of Pharmaceutical Sciences, Jerry H Hodge School of Pharmacy, Texas Tech University Health Sciences Center, 5920 Forest Park Road, Dallas, TX 75235, United States.
Int J Pharm. 2019 Oct 5;569:118596. doi: 10.1016/j.ijpharm.2019.118596. Epub 2019 Aug 5.
Epidemiological studies have compellingly documented the ability of the Mediterranean diet rich in extra-virgin olive oil to reduce the incidence of certain malignancies, and cardiovascular diseases, and slow the Alzheimer's disease progression. S-(-)-Oleocanthal (OC) was identified as the most bioactive olive oil phenolic with documented anti-inflammatory, anticancer, and anti-Alzheimer's activities. OC consumption causes irritating sensation at the oropharynx via activation of TRPA1. Accordingly, a taste-masked formulation of OC is needed for its future use as a nutraceutical while maintaining its bioactivity and unique chemistry. Therefore, the goal of this study was to prepare a taste-masked OC solid formulation with improved dissolution and pharmacodynamic profiles, by using (+)-xylitol as an inert carrier. Xylitol was hypothesized to serve as an ideal vehicle for the preparation of OC solid dispersions due to its low melting point and sweetness. The optimized OC-(+)-xylitol solid dispersion was physically and chemically characterized and showed effective taste masking and enhanced dissolution properties. Furthermore, OC-(+)-xylitol solid dispersion maintained potent in vivo anti-breast cancer activity. It effectively suppressed the human triple negative breast cancer development, growth, and recurrence after primary tumor surgical excision in nude mice orthotopic xenograft models. Collectively, these results suggest the OC-(+)-xylitol solid dispersion formulation as a potential nutraceutical for effective control and prevention of human triple negative breast cancer.
流行病学研究有力地证明了富含特级初榨橄榄油的地中海饮食能够降低某些恶性肿瘤、心血管疾病的发病率，并减缓阿尔茨海默病的进展。S-(-)-橄榄苦苷 (OC) 被确定为最具生物活性的橄榄油酚类化合物，具有抗炎、抗癌和抗阿尔茨海默病的作用。OC 通过激活 TRPA1 引起口腔咽部的刺激性感觉。因此，需要对 OC 进行掩味配方处理，以将其作为一种营养保健品使用，同时保持其生物活性和独特的化学性质。因此，本研究的目的是通过使用 (+)-木糖醇作为惰性载体来制备一种掩味 OC 固体配方，以改善其溶解和药效学特性。由于 (+)-木糖醇具有低熔点和甜味，因此假设它可作为 OC 固体分散体的理想载体。对优化的 OC-(+)-木糖醇固体分散体进行了物理和化学表征，结果表明其具有有效的掩味和增强的溶解性能。此外，OC-(+)-木糖醇固体分散体保持了有效的体内抗乳腺癌活性。它在裸鼠原位异种移植模型中有效抑制了人三阴性乳腺癌的发展、生长和原发性肿瘤切除后的复发。综上所述，这些结果表明 OC-(+)-木糖醇固体分散体配方可能是一种有效的营养保健品，可有效控制和预防人三阴性乳腺癌。
