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Engineered Cellular Uptake and Controlled Drug Delivery Using Two Dimensional Nanoparticle and Polymer for Cancer Treatment
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2018-01-18 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b01119
Sudipta Senapati 1 , Rashmi Shukla 2 , Yamini Bhusan Tripathi 2 , Arun Kumar Mahanta 1 , Dipak Rana 3 , Pralay Maiti 1
Affiliation  

Two major problems in chemotherapy, poor bioavailability of hydrophobic anticancer drug and its adverse side effects causing nausea, are taken into account by developing a sustained drug release vehicle along with enhanced bioavailability using two-dimensional layered double hydroxides (LDHs) with appropriate surface charge and its subsequent embedment in polymer matrix. A model hydrophobic anticancer drug, raloxifene hydrochloride (RH), is intercalated into a series of zinc iron LDHs with varying anion charge densities using an ion exchange technique. To achieve significant sustained delivery, drug-intercalated LDH is embedded in poly(ε-caprolactone) (PCL) matrix to develop intravenous administration and to improve the therapeutic index of the drug. The cause of sustained release is visualized from the strong interaction between LDH and drug, as measured through spectroscopic techniques, like X-ray photoelectron spectroscopy, infrared, UV–visible spectroscopy, and thermal measurement (depression of melting temperature and considerable reduction in heat of fusion), using differential scanning calorimeter, followed by delayed diffusion of drug from polymer matrix. Interestingly, polymer nanohybrid exhibits long-term and excellent in vitro antitumor efficacy as opposed to pure drug or drug-intercalated LDH or only drug embedded PCL (conventional drug delivery vehicle) as evident from cell viability and cell adhesion experiments prompting a model depicting greater killing efficiency (cellular uptake) of the delivery vehicle (polymer nanohybrid) controlled by its better cell adhesion as noticed through cellular uptake after tagging of fluorescence rhodamine B separately to drug and LDH. In vivo studies also confirm the sustained release of drug in the bloodstream of albino rats using polymer nanohybrid (novel drug delivery vehicle) along with a healthy liver vis-à-vis burst release using pure drug/drug-intercalated LDHs with considerable damaged liver.

中文翻译:

利用二维纳米粒子和聚合物对细胞进行工程化的细胞摄取和可控药物递送,以治疗癌症。

通过开发具有适当表面电荷的二维分层双氢氧化物(LDH)来开发持续释放药物的载体以及增强的生物利用度,可以考虑到化学疗法中的两个主要问题,即疏水性抗癌药物的生物利用度较差及其引起恶心的不良副作用。其随后嵌入聚合物基质中。使用离子交换技术将模型疏水性抗癌药物雷洛昔芬盐酸盐(RH)插入一系列具有不同阴离子电荷密度的锌铁LDH中。为了实现显着的持续递送,将药物嵌入的LDH嵌入聚(ε-己内酯)(PCL)基质中,以开发静脉内给药并改善药物的治疗指数。从LDH与药物之间的强相互作用可以看出持续释放的原因,通过差示扫描量热仪通过光谱技术(例如X射线光电子能谱,红外,紫外可见光谱和热测量(降低熔融温度并显着降低熔化热)进行测量,然后延迟药物从聚合物中扩散矩阵。有趣的是,聚合物纳米杂化物表现出长期且优异的性能。从细胞活力和细胞粘附实验中可以看出,与纯药物或药物嵌入的LDH或仅药物嵌入的PCL(常规药物传递载体)相反,体外抗肿瘤功效提示模型描绘了更高的杀伤效率(细胞吸收)(荧光罗丹明B分别标记为药物和LDH后,细胞摄取可注意到其具有更好的细胞粘附性。体内研究还证实,使用聚合物纳米杂化剂(新药递送载体)在白化病大鼠的血液中持续释放药物,以及使用具有严重受损肝的纯药物/插入药物的LDHs相对于健康的肝脏爆发释放。
更新日期:2018-01-18
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