State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Biomed Res Int. 2021 Apr 20;2021:5949804. doi: 10.1155/2021/5949804. eCollection 2021.
The clinical efficacy of Oxaliplatin (L-OHP) is potentially limited by dose-dependent neurotoxicity and high partitioning to erythrocytes . Long-circulating liposomes could improve the pharmacokinetic profile of L-OHP and thus enhance its therapeutic efficacy and reduce its toxicity. The purpose of this study was to prepare L-OHP long-circulating liposomes (L-OHP PEG lip) by reverse-phase evaporation method (REV) and investigate their pharmacokinetic behavior based on total platinum in rat plasma using atomic absorption spectrometry (AAS). A simple and a sensitive AAS method was developed and validated to determine the total platinum originated from L-OHP liposomes in plasma. Furthermore, long-circulating liposomes were fully characterized and showed great stability when stored at 4°C for one month. The results showed that the total platinum in plasma of L-OHP long-circulating liposomes displayed a biexponential pharmacokinetic profile with five folds higher bioavailability and longer distribution half-life compared to L-OHP solution. Thus, long-circulating liposomes prolonged L-OHP circulation time and may present a potential candidate for its tumor delivery. Conclusively, the developed AAS method could serve as a reference to investigate the pharmacokinetic behavior of total platinum in biological matrices for other L-OHP delivery systems.
奥沙利铂（L-OHP）的临床疗效可能受到剂量依赖性神经毒性和高红细胞分配的限制。长循环脂质体可以改善 L-OHP 的药代动力学特征，从而提高其治疗效果并降低其毒性。本研究旨在通过反相蒸发法（REV）制备奥沙利铂长循环脂质体（L-OHP PEG 脂质体），并基于原子吸收光谱法（AAS）在大鼠血浆中用总铂来研究其药代动力学行为。建立并验证了一种简单灵敏的 AAS 方法，用于测定来自血浆中 L-OHP 脂质体的总铂。此外，对长循环脂质体进行了充分的表征，并且在 4°C 下储存一个月时表现出很好的稳定性。结果表明，与 L-OHP 溶液相比，L-OHP 长循环脂质体在血浆中的总铂呈现双指数药代动力学特征，生物利用度提高了五倍，分布半衰期延长。因此，长循环脂质体延长了 L-OHP 的循环时间，可能成为其肿瘤递药的潜在候选物。总之，所开发的 AAS 方法可以作为研究其他 L-OHP 递药系统在生物基质中总铂药代动力学行为的参考。
