Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
Department of Pharmacy, Faculty of Pharmacy, Jadara University, 21110 Irbid, Jordan.
Molecules. 2020 Jul 15;25(14):3230. doi: 10.3390/molecules25143230.
The aim of this study was to prepare doxycycline polymeric nanoparticles (DOXY-PNPs) with hope to enhance its chemotherapeutic potential against solid Ehrlich carcinoma (SEC).
Three DOXY-PNPs were formulated by nanoprecipitation method using hydroxypropyl methyl cellulose (HPMC) as a polymer. The prepared DOXY-PNPs were evaluated for the encapsulation efficiency (EE%), the drug loading capacity, particle size, zeta potential (ZP) and the in-vitro release for selection of the best formulation. PNP number 3 was selected for further biological testing based on the best pharmaceutical characters. PNP3 (5 and 10 mg/kg) was evaluated for the antitumor potential against SEC grown in female mice by measuring the tumor mass as well as the expression and immunohistochemical staining for the apoptosis markers; caspase 3 and BAX.
The biological study documented the greatest reduction in tumor mass in mice treated with PNP3. Importantly, treatment with 5 mg/kg of DOXY-PNPs produced a similar chemotherapeutic effect to that produced by 10 mg/kg of free DOXY. Further, a significant elevation in mRNA expression and immunostaining for caspase 3 and BAX was detected in mice group treated with DOXY-PNPs.
The DOXY-PNPs showed greater antitumor potential against SEC grown in mice and greater values for Spearman's correlation coefficients were detected when correlation with tumor mass or apoptosis markers was examined; this is in comparison to free DOXY. Hence, DOXY-PNPs should be tested in other tumor types to further determine the utility of the current technique in preparing chemotherapeutic agents and enhancing their properties.
本研究旨在制备盐酸多西环素聚合物纳米粒（DOXY-PNPs），以期增强其对实体艾氏腹水癌（SEC）的化学治疗潜力。
采用纳米沉淀法，以羟丙甲纤维素（HPMC）为聚合物，制备了 3 种 DOXY-PNPs。对制备的 DOXY-PNPs 的包封效率（EE%）、载药量、粒径、Zeta 电位（ZP）和体外释放进行评价，以选择最佳制剂。根据最佳药学特性，选择 PNP 3 号进行进一步的生物学测试。根据肿瘤质量以及细胞凋亡标志物 caspase 3 和 BAX 的表达和免疫组织化学染色，评价 PNP3（5 和 10 mg/kg）对雌性小鼠 SEC 生长的抗肿瘤潜力。
生物学研究记录了用 PNP3 治疗的小鼠肿瘤质量的最大减少。重要的是，用 5mg/kg 的 DOXY-PNPs 治疗产生的化学治疗效果与 10mg/kg 的游离 DOXY 相似。此外，在用 DOXY-PNPs 治疗的小鼠组中，检测到 caspase 3 和 BAX 的 mRNA 表达和免疫染色显著升高。
DOXY-PNPs 对 SEC 在小鼠中的生长显示出更大的抗肿瘤潜力，并且当与肿瘤质量或细胞凋亡标志物相关时，检测到与 Spearman 相关系数的相关性更大；与游离 DOXY 相比。因此，应该在其他肿瘤类型中测试 DOXY-PNPs，以进一步确定当前技术在制备化疗药物和增强其特性方面的效用。
