Alshamrani Saad, Kumar Ashok, Aldughaim Mohammed S, Alghamdi Khalid M, Hussain Muhammad Delwar, Alanazi Fars K, Kazi Mohsin
Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
Vitiligo Research Chair, Department of Dermatology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
J Cancer. 2024 Jul 8;15(14):4717-4730. doi: 10.7150/jca.96402. eCollection 2024.
Luteolin (LUT) is a bioactive compound with several pharmacological activities including anticancer effect. Doxorubicin (DOX) is an anthracycline chemotherapeutic drug that have proven to be effective in treating various types of cancers. Polymeric micelles (PMs) containing biologically active materials have emerged as prospective dosage forms with high drug-loading, which can add therapeutic benefit to the poorly water-soluble compounds and novel chemical entities. PMs are effective in delivering several drugs, such as anticancer drugs, antifungal drugs, flavonoids and drugs targeting the brain. The aim of the current study is to develop PMs for LUT and DOX as a combined delivery system for cancer therapy. PMs were prepared using 2.5% of each of LUT and DOX with varying compositions of Poloxamer 188, Poloxamer 407, Vitamin E (TPGS), Poloxamer 123 and Gellucire 44/14 at room temperature. Particle size, polydispersity index, zeta potential, were achieved using Zetasizer Nano particle size analyzer and the sizes were further confirmed with transmission electron microscopy (TEM). Prepared PMs were further characterized using powder X-ray diffraction (PXRD) and fourier transform infrared spectroscopy (FTIR). An MTT assay was performed on breast cancer (MCF-7) cells and liver cancer (HepG2) cells to determine the cytotoxic effect of the different PMs formulations. PMs were successfully developed and optimized using 74.3% Poloxamer 407 with 20.7% Vitamin E (TPGS), and 70% Poloxamer 407 with 25% Gellucire 44/14, respectively. The droplet size and polydispersity index were found to be 62.03 ± 3.99 nm, 91.96 ± 5.80 nm and 0.33 ± 0.05, 0.59± 0.03, respectively for PMs containing TPGS and Gellucire 44/14. Zeta potentials of the PMs containing TPGS and Gellucire 44/14 were recorded as -2.27 ±0.11mV and -7.78 ± 0.10 mV, respectively. The PMs showed a spherical structure with approximately 50-90 nm range evident by TEM analysis. The PXRD spectra of PMs powder presented the amorphization of LUT and DOX. The FTIR spectra of LUT-loaded and DOX-loaded PMs were identical, suggesting consistent PMs composition. The MTT assay showed that the representative combined drug loaded PMs treatment led to a reduction in the viability of MCF-7 and HepG2 cells compared to drug free PMs and pure LUT, DOX alone. PMs with LUT and DOX exhibited significant cytotoxic effects against breast and liver cancer cells and could thus be an important new pharmaceutical formulation to treat cancer.
木犀草素（LUT）是一种具有多种药理活性的生物活性化合物，包括抗癌作用。阿霉素（DOX）是一种蒽环类化疗药物，已被证明对治疗各种类型的癌症有效。含有生物活性材料的聚合物胶束（PMs）已成为具有高载药量的潜在剂型，可为水溶性差的化合物和新型化学实体增加治疗益处。PMs在递送多种药物方面有效，如抗癌药物、抗真菌药物、黄酮类化合物以及靶向脑部的药物。本研究的目的是开发用于LUT和DOX的PMs作为癌症治疗的联合递送系统。在室温下，使用2.5%的LUT和DOX以及不同组成的泊洛沙姆188、泊洛沙姆407、维生素E（TPGS）、泊洛沙姆123和Gelucire 44/14制备PMs。使用Zetasizer Nano粒度分析仪测定粒径、多分散指数和zeta电位，并用透射电子显微镜（TEM）进一步确认粒径。使用粉末X射线衍射（PXRD）和傅里叶变换红外光谱（FTIR）对制备的PMs进行进一步表征。对乳腺癌（MCF-7）细胞和肝癌（HepG2）细胞进行MTT试验，以确定不同PMs制剂的细胞毒性作用。分别使用74.3%的泊洛沙姆407与20.7%的维生素E（TPGS）以及70%的泊洛沙姆407与25%的Gelucire 44/14成功开发并优化了PMs。发现含有TPGS和Gelucire 44/14的PMs的液滴尺寸和多分散指数分别为62.03±3.99nm、91.96±5.80nm和0.33±0.05、0.59±0.03。含有TPGS和Gelucire 44/14的PMs的zeta电位分别记录为-2.27±0.11mV和-7.78±0.10mV。通过TEM分析，PMs呈现出约50-90nm范围的球形结构。PMs粉末的PXRD光谱显示LUT和DOX非晶化。负载LUT和DOX的PMs的FTIR光谱相同，表明PMs组成一致。MTT试验表明，与不含药物的PMs和单独的纯LUT、DOX相比，代表性的联合载药PMs处理导致MCF-7和HepG2细胞活力降低。含有LUT和DOX的PMs对乳腺癌和肝癌细胞表现出显著的细胞毒性作用，因此可能是一种治疗癌症的重要新药物制剂。
