Abstract Letrozole (LET), an aromatase inhibitor widely used as a first-line drug for the estrogen-dependent breast cancer treatment in postmenopausal women. In this study, an attempt has been made to develop LET topical drug delivery which would be a more efficient system to treat elevated blood levels of estrogen found in breast cancer patients. The technique involves, encapsulation of the LET in phospholipids using spray dryer. The LET spray-dried powder (LT-SDP) powder was tested by Fourier transform infrared, X-RD, and differential scanning calorimetry. These studies confirm the entrapment efficiency (EE) of the system. The LT-SDP in the form dispersion was further evaluated. The confocal laser scanning microscopy (CLSM) showed spherical vesicles, the particle size, polydispersity index, and the EE was found to be 284.0 nm, 0.247, and 59.08%, respectively. LT-SDP dispersion was added into a cream base with peppermint and olive oil as natural penetration enhancers. Optimized formulation showed superior skin targeting in in vitro and in vivo studies. Cell proliferation assay and flow cytometry was carried out using human cancer cell line of breast MDA-MB-231 which showed superior anti-proliferative action and enhanced apoptosis activity of LT-SDP cream (43.9%) in comparison. The CLSM micrograph, skin irritation, and histopathology studies showed the penetration ability and inertness of the LT-SDP cream, respectively. In vivo bioavailability studies showed an almost four-fold increase in the plasma concentration (11.3 versus 4.2) while the mean residence time (81.11 versus 64.42 h) and half-life (51.01 versus 39.36 h) were reasonably higher than plain LET cream.

中文翻译：

---

用于局部应用的带有 PE 的负载来曲唑喷雾干燥脂质体的配方和评价

摘要 来曲唑（LET）是一种芳香化酶抑制剂，广泛用作绝经后妇女雌激素依赖性乳腺癌治疗的一线药物。在这项研究中，已经尝试开发 LET 局部给药，这将是一种更有效的系统，用于治疗乳腺癌患者体内雌激素升高的血液水平。该技术涉及使用喷雾干燥器将 LET 封装在磷脂中。LET 喷雾干燥粉末 (LT-SDP) 粉末通过傅里叶变换红外、X-RD 和差示扫描量热法进行测试。这些研究证实了系统的截留效率 (EE)。进一步评估呈分散体形式的LT-SDP。共聚焦激光扫描显微镜 (CLSM) 显示球形囊泡，粒径、多分散指数和 EE 为 284.0 nm、0.247 和 59.08%，分别。将 LT-SDP 分散体添加到含有薄荷和橄榄油作为天然渗透促进剂的奶油基质中。优化的配方在体外和体内研究中显示出卓越的皮肤靶向性。使用人乳腺癌细胞系 MDA-MB-231 进行细胞增殖测定和流式细胞术，相比之下，LT-SDP 乳膏显示出优异的抗增殖作用和增强的细胞凋亡活性 (43.9%)。CLSM 显微照片、皮肤刺激和组织病理学研究分别显示了 LT-SDP 乳膏的渗透能力和惰性。体内生物利用度研究表明血浆浓度增加了近四倍（11.3 对 4.2），而平均停留时间（81.11 对 64.42 小时）和半衰期（51.01 对 39.36 小时）比普通 LET 乳膏合理地高。将 LT-SDP 分散体添加到含有薄荷和橄榄油作为天然渗透促进剂的奶油基质中。优化的配方在体外和体内研究中显示出卓越的皮肤靶向性。使用人乳腺癌细胞系 MDA-MB-231 进行细胞增殖测定和流式细胞术，相比之下，LT-SDP 乳膏显示出优异的抗增殖作用和增强的细胞凋亡活性 (43.9%)。CLSM 显微照片、皮肤刺激和组织病理学研究分别显示了 LT-SDP 乳膏的渗透能力和惰性。体内生物利用度研究显示血浆浓度增加了近四倍（11.3 对 4.2），而平均停留时间（81.11 对 64.42 小时）和半衰期（51.01 对 39.36 小时）比普通 LET 乳膏合理地高。将 LT-SDP 分散体添加到含有薄荷和橄榄油作为天然渗透促进剂的奶油基质中。优化的配方在体外和体内研究中显示出卓越的皮肤靶向性。使用人乳腺癌细胞系 MDA-MB-231 进行细胞增殖测定和流式细胞术，相比之下，LT-SDP 乳膏显示出优异的抗增殖作用和增强的细胞凋亡活性 (43.9%)。CLSM 显微照片、皮肤刺激和组织病理学研究分别显示了 LT-SDP 乳膏的渗透能力和惰性。体内生物利用度研究显示血浆浓度增加了近四倍（11.3 对 4.2），而平均停留时间（81.11 对 64.42 小时）和半衰期（51.01 对 39.36 小时）比普通 LET 乳膏合理地高。