Raloxifene (RLX), a biopharmaceutical classification system (BCS) class II drug, is a selective estrogen receptor modulator (SERM) having an estrogenic effect on the bone and an antiestrogenic effect on the endometrium and breast. Low solubility, high permeability, high metabolism, and low bioavailability are the characteristics of raloxifene. Although 60% is absorbed orally, raloxifene shows extremely poor bioavailability (2%) owing to its low solubility and extensive (>90%) intestinal/hepatic first-pass metabolism. Hence, it becomes important to increase the solubility of raloxifene to enhance its bioavailability. In this study, raloxifene nanostructured lipid carriers (RNLCs) were prepared using the melt dispersion ultrasonication method. The prepared RNLCs were characterized, and the in vitro studies were carried out in the human epithelial breast cancer cell line (MCF-7). The RNLCs had a size of 114.8 ± 0.98 nm and a zeta potential of +9.21 ± 0.58 mV. Transmission electron microscopy (TEM) images showed particle size ranging from 65 to 120 nm. With an entrapment efficiency of 75.04% ± 2.75%, the RNLCs showed sustained release over 7 days compared with the raloxifene drug solution. The prepared RNLCs were successfully taken up by the MCF-7 cells in a time-dependent manner, and the RNLCs showed increased cell cytotoxicity compared with the raloxifene drug. Using the parallel artificial membrane permeability assay (PAMPA), the permeability rate for raloxifene solution was calculated to be 8 × 10⁻⁶ cm/s, and for the RNLCs, it was calculated to be 17.8 × 10⁻⁶ cm/s. Hence, from the permeability rate calculated, we could conclude that raloxifene, when formulated as nanostructured lipid carriers, showed increased permeability. Overall, the prepared RNLCs were found to be superior to the raloxifene drug as such.

中文翻译：

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用于渗透性和吸收增强应用的雷洛昔芬纳米结构脂质载体的配方和表征

雷洛昔芬 (RLX) 是一种生物制药分类系统 (BCS) II 类药物，是一种选择性雌激素受体调节剂 (SERM)，对骨骼具有雌激素作用，对子宫内膜和乳房具有抗雌激素作用。低溶解度、高渗透性、高代谢、低生物利用度是雷洛昔芬的特点。虽然 60% 被口服吸收，但雷洛昔芬显示出极差的生物利用度 (2%)，这是由于其低溶解度和广泛 (>90%) 的肠/肝首过代谢。因此，增加雷洛昔芬的溶解度以提高其生物利用度变得很重要。本研究采用熔体分散超声法制备雷洛昔芬纳米结构脂质载体（RNLCs）。对制备的 RNLC 进行表征，并在体外在人上皮乳腺癌细胞系（MCF-7）中进行了研究。RNLC 的大小为 114.8 ± 0.98 nm，zeta 电位为 +9.21 ± 0.58 mV。透射电子显微镜 (TEM) 图像显示粒径范围为 65 至 120 nm。与雷洛昔芬药物溶液相比，RNLCs 的包封率为 75.04% ± 2.75%，可在 7 天内持续释放。制备的RNLCs以时间依赖性方式成功地被MCF-7细胞吸收，与雷洛昔芬药物相比，RNLCs的细胞毒性增加。使用平行人工膜渗透性测定法(PAMPA)，计算雷洛昔芬溶液的渗透率为8×10 ^-6 cm/s，对于RNLC，计算为17.8×10 ^-6厘米/秒。因此，根据计算的渗透率，我们可以得出结论，雷洛昔芬在配制成纳米结构的脂质载体时，显示出增加的渗透性。总体而言，发现制备的 RNLC 优于雷洛昔芬药物。