Centre for Nanosciences & Molecular Medicine, Amrita Institute of Medical Sciences & Research Centre, Amrita Viswavidyapeetham, Kochi, Kerala, 682041, India.
Drug Deliv Transl Res. 2019 Oct;9(5):867-878. doi: 10.1007/s13346-018-00614-x.
This study reports the development of a nanoformulation of diclofenac sodium, a potent non-steroidal anti-inflammatory drug, at its clinical dose, utilizing a FDA approved polymer, hydroxyethyl starch. The study specifically focused on the control of pharmacokinetics, pharmacodynamics, and biodistribution by particle surface functionalization and alteration of excipient levels in the final formulation. Stable diclofenac sodium-loaded hydroxyethyl starch nanoparticles (nanodiclo) of size 170 ± 5 nm and entrapment efficiency 72 ± 3% were prepared. Free diclofenac, nanodiclo, nanodiclo surface functionalized by PEGylation, nanodiclo with excipients removed, and finally PEGylated nanodiclo with excipients removed were all tested comparatively at two different doses. The results showed substantial impact of both excipients and PEGylation on the pharmacokinetics and pharmacodynamics in vivo. Further, the results proved that excipient removed PEGylated nanodiclo at lower dose achieved clinical therapeutic levels in blood for up to 120 h, with minimal accumulation in critical organs, and much better efficacy than other controls.
本研究报告了一种将临床剂量的双氯芬酸钠（一种强效的非甾体抗炎药）纳米制剂化的方法，该制剂使用了一种经美国食品和药物管理局批准的聚合物——羟乙基淀粉。研究特别关注通过颗粒表面功能化和改变最终制剂中赋形剂水平来控制药代动力学、药效学和生物分布。成功制备了粒径为 170±5nm，包封率为 72±3%的稳定双氯芬酸钠载羟乙基淀粉纳米粒（纳米双氯芬酸钠）。分别对游离双氯芬酸钠、纳米双氯芬酸钠、经 PEG 化表面功能化的纳米双氯芬酸钠、去除赋形剂的纳米双氯芬酸钠和去除赋形剂的 PEG 化纳米双氯芬酸钠进行了比较测试，采用了两种不同剂量。结果表明，赋形剂和 PEG 化对体内药代动力学和药效学有显著影响。此外，结果证明，较低剂量下去除赋形剂的 PEG 化纳米双氯芬酸钠在血液中达到临床治疗水平长达 120 小时，在关键器官中积累最小，疗效明显优于其他对照组。
