Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia,
Int J Nanomedicine. 2019 Mar 1;14:1587-1595. doi: 10.2147/IJN.S195048. eCollection 2019.
Apremilast (APM) is a novel, orally administered small molecule drug approved for treatment of psoriasis or psoriatic arthritis. Due to its low solubility and permeability, it is classified as a class IV drug according to BCS classification. Dose titration is recommended during APM treatment due to its tolerability and twice-daily dosing regimen issues.
In this study, three different APM-loaded PLGA nanoparticles (F1-F3) were prepared by single emulsion and evaporation method. Based on particle size, PDI, zeta potential (ZP), entrapment efficiency (%EE), drug loading (%DL), and spectral characterization, the nanoparticles (F3) were optimized. The F3 nanoparticles were further evaluated for in vitro release and in vivo pharmacokinetic studies in rats.
The optimized nanoparticles (F3) had particles size 307.3±8.5 nm with a low PDI value 0.317, ZP of -43.4±2.6 mV, EE of 61.1±1.9% and DL of 1.9±0.1%. The in vitro release profile showed a sustained release pattern of F3 nanoparticles of APM. The pharmacokinetic results showed 2.25 times increase in bio-availability of F3 nanoparticles compared to normal APM suspension. Moreover, significant increase in half-life and mean residence time confirms long-term retention of F3 nanoparticles.
Bioavailability enhancement along-with long-term retention of the APM-loaded PLGA nanoparticles might be helpful for the once-daily regimen treatment.
阿普斯特（APM）是一种新型的、口服小分子药物，用于治疗银屑病或银屑病关节炎。由于其低溶解度和通透性，根据 BCS 分类，它被归类为 IV 类药物。由于其耐受性和每日两次给药方案的问题，建议在 APM 治疗中进行剂量滴定。
在这项研究中，通过单乳液和蒸发法制备了三种不同的载有 APM 的 PLGA 纳米粒（F1-F3）。基于粒径、PDI、Zeta 电位（ZP）、包封效率（%EE）、载药量（%DL）和光谱特性，对纳米粒（F3）进行了优化。进一步对 F3 纳米粒进行了体外释放和大鼠体内药代动力学研究。
优化后的纳米粒（F3）粒径为 307.3±8.5nm，PDI 值低至 0.317，ZP 为-43.4±2.6mV，EE 为 61.1±1.9%，DL 为 1.9±0.1%。体外释放曲线显示 F3 纳米粒的 APM 呈现持续释放模式。药代动力学结果表明，与普通 APM 混悬剂相比，F3 纳米粒的生物利用度提高了 2.25 倍。此外，半衰期和平均停留时间的显著增加证实了 F3 纳米粒的长期保留。
APM 载 PLGA 纳米粒的生物利用度提高和长期保留可能有助于每日一次的治疗方案。
