Yadav Pooja, Chauhan Divya, Yadav Pavan Kumar, Kashyap Amit, Gayen Jiaur R, Chourasia Manish K
Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
Bioanalysis. 2025 Aug;17(16):1017-1029. doi: 10.1080/17576180.2025.2548198. Epub 2025 Aug 25.
Oral metronomic chemotherapy employs a low-dose combination of chemotherapeutics administered regularly to minimize toxicity while enhancing anticancer efficacy. The clinical utility of Doxorubicin (DOX) is limited due to severe cardiotoxicity. Interestingly, Piperine (PIP) has been explored to mitigate DOX-induced toxicity while enhancing its therapeutic efficacy. Solid lipid nanoparticles (SLNs) offer an efficient drug delivery approach to improve oral bioavailability and controlled release of DOX and PIP.
LC-MS/MS method was developed and validated per US-FDA bioanalytical guidelines to quantify DOX and PIP in plasma simultaneously. SLNs were developed and optimized using design expert software and exhibited particle size of 151.56 ± 0.32 nm, polydispersity index (PDI) of 0.172 ± 0.02, and surface charge of -22.83 ± 0.66 mV. Pharmacokinetic evaluation in female Sprague-Dawley rats showed enhanced AUC₀-∞ for DOX (31911.78 ± 226.92 ng/mL) and PIP (7377.66 ± 655.78 ng/mL), indicating improved systemic exposure.
The findings highlight the potential of SLN-based co-delivery of DOX and PIP for oral metronomic chemotherapy. The validated LC-MS/MS method ensures precise pharmacokinetic assessment, which is crucial for future clinical translation. This study provides a promising strategy for enhancing oral chemotherapy efficacy.
口服节拍化疗采用低剂量化疗药物联合定期给药，以尽量减少毒性，同时提高抗癌疗效。由于严重的心脏毒性，阿霉素（DOX）的临床应用受到限制。有趣的是，胡椒碱（PIP）已被探索用于减轻DOX诱导的毒性，同时提高其治疗效果。固体脂质纳米粒（SLNs）提供了一种有效的药物递送方法，可提高DOX和PIP的口服生物利用度和控释。
根据美国食品药品监督管理局（US-FDA）生物分析指南开发并验证了LC-MS/MS方法，用于同时定量血浆中的DOX和PIP。使用设计专家软件开发并优化了SLNs，其粒径为151.56±0.32nm，多分散指数（PDI）为0.172±0.02，表面电荷为-22.83±0.66mV。对雌性Sprague-Dawley大鼠的药代动力学评估显示，DOX（31911.78±226.92ng/mL）和PIP（7377.66±655.78ng/mL）的AUC₀-∞增加，表明全身暴露得到改善。
研究结果突出了基于SLN的DOX和PIP联合递送用于口服节拍化疗的潜力。经过验证的LC-MS/MS方法确保了精确的药代动力学评估，这对未来的临床转化至关重要。本研究为提高口服化疗疗效提供了一种有前景的策略。
