Ahmad Niyaz, Ahmad Rizwan, Alam Md Aftab, Ahmad Farhan Jalees
Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam, 31441, Kingdom of Saudi Arabia.
Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia.
Chem Cent J. 2018 May 23;12(1):65. doi: 10.1186/s13065-018-0434-1.
Doxorubicin hydrochloride (DOX·HCl), an anthracycline glycoside antibiotic, exhibits low oral bioavailability due to active efflux from intestinal P-glycoprotein receptors. The oral administration of DOX remains a challenge hence; no oral formulation for DOX is marketed, till date.
To improve the oral bioavailability of DOX through, preparation of a nanoformulation i.e. PEGylated-doxorubicin(DOX)-loaded-poly-lactic-co-glycolic acid (PLGA)-Nanoparticles (NPs) and to develop and validate an ultra-high performance liquid chromatography electrospray ionization-synapt mass spectrometric bioanalytical method (UHPLC/ESI-QTOF-MS/MS) for plasma (Wistar rats) DOX quantification.
For chromatography, Waters ACQUITY UPLC™ along with a BEH C-18 column (2.1 mm × 100 mm; 1.7 μm), mobile phase conditions (acetonitrile: 0.1% formic acid::1:1 v/v) and flow rate (0.20 ml/min) was used. For analyte recovery from rat plasma, a liquid-liquid extraction method (LLE), using Acetonitrile: 5 mM ammonium acetate in a ratio of 6:4 v/v at pH 3.5, was used.
Nanoformulation with a particle size (183.10 ± 7.41 nm), zeta potential (- 13.10 ± 1.04 mV), drug content (42.69 ± 1.97 µg/mg) and a spherical shape and smooth surface was developed. An elution time of 1.61 and 1.75 min along with a transition at m/z 544.42/397.27 and 528.46/321.41 were observed for DOX and internal standard (IS) Daunorubicin, respectively. In addition, a linear dynamic range with r ≥ 0.9985 over a concentration range of 1.00-2500.0 ng/ml was observed for different processes and parameters used in the study. Similarly a marked improvement i.e. 6.8 fold was observed, in PEGylated-DOX-PLGA-NPs as compared to DOX-S, in pharmacokinetics studies.
The promising approach of PEGylated-DOX-PLGA-NPs may provide an alternate to intravenous therapy for better patient care.
盐酸多柔比星（DOX·HCl）是一种蒽环类糖苷抗生素，由于其从肠道P-糖蛋白受体的主动外排，口服生物利用度较低。因此，DOX的口服给药仍然是一个挑战；迄今为止，尚无DOX的口服制剂上市。
通过制备纳米制剂，即聚乙二醇化多柔比星（DOX）负载的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒（NPs）来提高DOX的口服生物利用度，并开发和验证一种用于血浆（Wistar大鼠）中DOX定量的超高效液相色谱电喷雾电离-同步加速器质谱生物分析方法（UHPLC/ESI-QTOF-MS/MS）。
色谱分析采用Waters ACQUITY UPLC™ 及BEH C-18柱（2.1 mm×100 mm；1.7 µm），流动相条件为（乙腈：0.1%甲酸::1:1 v/v），流速为0.20 ml/min。对于从大鼠血浆中回收分析物，采用液液萃取法（LLE），使用乙腈：5 mM醋酸铵，比例为6:4 v/v，pH值为3.5。
制备出了粒径为（183.10±7.41 nm）、ζ电位为（-13.10±1.04 mV）、药物含量为（42.69±1.97 µg/mg）且呈球形且表面光滑的纳米制剂。观察到DOX和内标柔红霉素的洗脱时间分别为1.61和1.75 min，m/z 544.42/397.27和528.46/321.41处有跃迁。此外，在该研究中使用的不同过程和参数下，在1.00 - 2500.0 ng/ml的浓度范围内观察到线性动态范围，r≥0.9985。同样，在药代动力学研究中，与DOX-S相比，聚乙二醇化DOX-PLGA-NPs有显著改善，即提高了6.8倍。
聚乙二醇化DOX-PLGA-NPs这种有前景的方法可能为更好的患者护理提供一种替代静脉治疗的方案。
