Thomas Shindu C, Madaan Tushar, Iqbal Zeenat, Talegaonkar Sushama
Nanoformulation Research Lab, Department of Pharmaceutics, School of Pharmaceutical Education & Research (formerly Faculty of Pharmacy), Jamia Hamdard, New Delhi-110062, India.
Department of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, Sector 3, New Delhi-110017, India.
Curr Drug Deliv. 2018;15(9):1230-1244. doi: 10.2174/1567201815666180620123347.
Bendamustine HCl, an antineoplastic drug, has a very short life of about 40 minutes which necessitates administration of large doses which leads to increased side effects as well as costs.
The present work describes the fabrication, optimization, and evaluation of bioactive hydroxyapatite nanoparticles to achieve sustained delivery of bendamustine HCl.
Hydroxyapatite nanoparticles (NPs) were prepared by the wet chemical precipitation method by reacting a calcium and phosphate precursor and the reaction was optimized via Box-Behnken DOE. The drug was loaded on particles by physical adsorption. Various analytical studies were performed on the fabricated nanoparticles in addition to biodistribution studies to establish the physicochemical and biological characteristics of the designed formulation.
pH of the reactant solution was found to have a more profound effect on the particle size and size distribution in comparison to reactant concentration. The particles were found to have a spherical morphology by SEM. Size of the blank and drug-loaded nanoparticles was found to be 130±20 nm by TEM. Energy Dispersive X-ray Spectroscopy (EDS) studies confirmed the presence of hydroxyapatite as the dominant phase while DSC studies indicated the presence of the drug in its amorphous form after its adsorption on NPs. Tissue distribution studies further suggested that the majority of drug concentration was released in blood rather than the other organs implying low organ toxicity.
Bendamustine loaded hydroxyapatite nanoparticles were successfully optimized and fabricated. Favorable results were obtained in in vitro, in vivo, and analytical studies.
盐酸苯达莫司汀是一种抗肿瘤药物，其半衰期非常短，约为40分钟，这就需要大剂量给药，从而导致副作用增加以及成本上升。
本研究描述了生物活性羟基磷灰石纳米颗粒的制备、优化及评价，以实现盐酸苯达莫司汀的持续释放。
通过钙和磷酸盐前驱体反应，采用湿化学沉淀法制备羟基磷灰石纳米颗粒（NPs），并通过Box-Behnken实验设计对反应进行优化。药物通过物理吸附负载在颗粒上。除了生物分布研究外，还对制备的纳米颗粒进行了各种分析研究，以确定所设计制剂的物理化学和生物学特性。
与反应物浓度相比，发现反应物溶液的pH值对粒径和粒径分布有更显著的影响。通过扫描电子显微镜（SEM）发现颗粒具有球形形态。通过透射电子显微镜（TEM）发现空白纳米颗粒和载药纳米颗粒的尺寸为130±20 nm。能量色散X射线光谱（EDS）研究证实羟基磷灰石是主要相，而差示扫描量热法（DSC）研究表明药物吸附在纳米颗粒上后以无定形形式存在。组织分布研究进一步表明，大部分药物浓度在血液中释放，而不是在其他器官中，这意味着器官毒性较低。
成功优化并制备了载有盐酸苯达莫司汀的羟基磷灰石纳米颗粒。在体外、体内和分析研究中均获得了良好的结果。
