Ghimire Biwash, Giri Pradeep, Mateen Sameena, Pashikanti Srinath, Aghazadeh-Habashi Ali
College of Pharmacy, Idaho State University, Pocatello, ID 83209, USA.
Pharmaceutics. 2025 Jun 22;17(7):807. doi: 10.3390/pharmaceutics17070807.
: Jaspine B, a synthetic analog of anhydrophytosphingosine, demonstrates significant anticancer activity; however, its clinical application is hindered by its poor oral bioavailability, resulting in suboptimal systemic exposure. This study aimed to enhance the pharmacokinetic properties of Jaspine B by developing a liposomal delivery system. : Jaspine B-loaded liposomes were formulated using a microfluidic approach and characterized by transmission electron microscopy (TEM) to assess particle morphology and size distribution. A sensitive and selective LC-MS/MS assay was developed and fully validated to quantify Jaspine B in rat plasma. The assay revealed excellent linearity across a broad concentration range and high intra- and inter-day precision. A pharmacokinetic study was conducted in Sprague Dawley rats to evaluate the influence of liposomal encapsulation on the pharmacokinetic profile of Jaspine B. : The liposomal formulation accelerated the absorption of Jaspine B, reaching the maximum concentration (T) at 2 h as opposed to 6 h in plain Jaspine B. The half-life (t) increased significantly from 7.9 ± 2.3 h to 26.7 ± 7.3 h. The area under the curve (AUC) increased over two-fold from 56.8 ± 12.3 ng.h/mL to 139.7 ± 27.2 ng.h/mL, suggesting increased systemic drug exposure. Similarly, the drug molecule's mean residence time (MRT) increased over three-fold. : These results indicate that liposomal formulation enhances the pharmacokinetics of Jaspine B, prolonging its body circulation and exposure, which explains the improved therapeutic outcomes we observed in our previous pharmacodynamic study.
茉莉宁B是脱水植物鞘氨醇的合成类似物，具有显著的抗癌活性；然而，其口服生物利用度差，导致全身暴露不理想，从而阻碍了其临床应用。本研究旨在通过开发脂质体递送系统来增强茉莉宁B的药代动力学性质。采用微流控方法制备了负载茉莉宁B的脂质体，并通过透射电子显微镜（TEM）对其进行表征，以评估颗粒形态和大小分布。开发并完全验证了一种灵敏且选择性高的液相色谱-串联质谱（LC-MS/MS）分析法，用于定量大鼠血浆中的茉莉宁B。该分析法在很宽的浓度范围内显示出良好的线性以及较高的日内和日间精密度。在Sprague Dawley大鼠中进行了药代动力学研究，以评估脂质体包封对茉莉宁B药代动力学特征的影响。脂质体制剂加速了茉莉宁B的吸收，在2小时时达到最大浓度（T），而普通茉莉宁B在6小时时达到最大浓度。半衰期（t）从7.9±2.3小时显著增加到26.7±7.3小时。曲线下面积（AUC）从56.8±12.3 ng·h/mL增加了两倍多，达到139.7±27.2 ng·h/mL，表明全身药物暴露增加。同样，药物分子的平均驻留时间（MRT）增加了三倍多。这些结果表明，脂质体制剂增强了茉莉宁B的药代动力学，延长了其在体内的循环和暴露时间，这解释了我们在之前的药效学研究中观察到的治疗效果改善的原因。
