生物利用度
药理学
药物输送
药代动力学
化学
前列腺癌
医学
癌症
内科学
有机化学
作者
Saurabh Shah,Paras Famta,Ganesh Vambhurkar,Dadi A. Srinivasarao,Kondasingh Charan Kumar,Deepkumar Bagasariya,Nusrat Begum,Anamika Sharma,Naitik Jain,Syed Shahrukh,Gurpreet Singh,Akshay Shinde,S. Prasad,Dharmendra Kumar Khatri,Saurabh Srivastava
标识
DOI:10.1016/j.jddst.2023.105052
摘要
Ibrutinib (IB), which is conventionally employed for leukemia exhibits poor aqueous solubility, poor oral bioavailability and significant food effect with a 2.15-fold increment in bioavailability in the presence of food act as barriers in its clinical translation. This creates a dilemma for the physician in estimating the dose and dosing regimen in patients. This dilemma could either result in sub-therapeutic efficacy or untoward adverse effects depending on the fasted or fed state of administration. The repurposing potential of IB and IB-loaded self-nanoemulsifying drug delivery systems (SNEDDS) in prostate cancer (PCa) has also not been explored yet. In this article, we have explored the potential of IB-SNEDDS for diminishing the pharmacokinetic food effect of IB and enhancement of its activity against PCa cells. Quality by design was utilized for the optimization of IB-SNEDDS. In vitro release studies showed a superior dissolution profile with rapid release in bio-relevant media compared to free IB. Cell culture studies revealed the safety of blank SNEDDS against Caco-2 cells and PC-3 cells. IB-SNEDDS revealed remarkable cytotoxic potential, ROS generation and apoptosis against PC-3 cells. Ex vivo intestinal permeation study confirmed the permeation of C-6 tagged SNEDDS globules across the intestinal barrier. The superior pharmacokinetic profile of IB-SNEDDS with AUCfast/fed (0.8476), while Cmaxfast/fed was (0.9375) being closer to 1 for SNEDDS reveals the circumvention of fast-fed variability.
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