醋酸阿比特龙 (ABA) 是一种 IV 类生物制药药物，其溶解度和渗透性存在缺陷，导致其口服生物利用度有限，并且具有积极的食物效应，即在食物存在的情况下药物吸收成倍增强。这给医生估计有效治疗前列腺癌（PCa）所需的剂量和剂量方案带来了困难。纳米结构脂质载体（NLC）在增强各种实体的口服生物利用度以及减弱食物效应方面已显示出巨大的成果。在本研究中，采用质量源于设计和多变量分析来优化 ABA 加载的 NLC (ABA NLC)。使用 QbD 获得的最佳尺寸、PDI 和 zeta 电位分别为 134.6 nm、0.163 和 -15.7 mV。离体定性和定量肠道通透性研究表明 NLC 通过肠段的移动性得到改善。生物相关的禁食和进食胃和肠介质中的体外溶出曲线显示，ABA NLC 与 ABA 相比差异极小。通过体内药代动力学来解读 ABA NLC 在减轻 ABA 食物效应方面的功效。研究表明，与游离 ABA 相比，禁食和进食状态下口服生物利用度分别提高了 14.51 倍和 1.94 倍。 ABA NLC 的吸收机制采用乳糜微粒流动阻断方法，以淋巴摄取为主要机制。 Cmax 空腹/进食比为 0.9758，而 AUC 空腹/进食比为 0.9386，几乎相等，证实了食物效应衰减。因此，研究结果证明了 ABA NLC 的最佳药代动力学及其在规避快速喂养变异性方面的效用。© 2024。控释协会。

Abiraterone acetate (ABA), a biopharmaceutical class IV drug suffers from solubility and permeability pitfalls resulting in limited oral bioavailability and positive food effect, i.e. multi-fold enhancement in drug absorption in the presence of food. This poses difficulties to physicians towards the estimation of dose and dosage regimen required for efficacious therapy of prostate cancer (PCa). Nanostructured lipid carriers (NLC) have demonstrated tremendous outcomes in enhancing the oral bioavailability of various entities along with food effect attenuation. In this study, Quality by design and multivariate analysis was employed for optimization of ABA loaded NLC (ABA NLC). The optimal size, PDI and zeta potential obtained using QbD were 134.6 nm, 0.163 and -15.7 mV respectively. Ex vivo qualitative and quantitative intestinal permeability studies demonstrated improved traversion of NLC through the intestinal segments. In vitro dissolution profile in biorelevant fast and fed gastric and intestinal media revealed minimal differences for ABA NLC compared to ABA. In vivo pharmacokinetics was performed to decipher the efficacy of ABA NLC in mitigating the food effect of ABA. The studies demonstrated 14.51-fold and 1.94-fold improvement in oral bioavailability during fasted and fed state respectively as compared to free ABA. The absorption mechanism of ABA NLC using chylomicron flow blocking approach conveyed lymphatic uptake as the major mechanism. Cmax fast/fed ratio was 0.9758 whereas, AUC fast/fed ratio was 0.9386, which being nearly equivalent, confirmed the food effect attenuation. Therefore, the results of the study demonstrate optimal pharmacokinetics of ABA NLC and its utility in circumventing the fast fed variability.© 2024. Controlled Release Society.