a Department of Pharmaceutics , College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University , Dammam , Kingdom of Saudi Arabia.
b Department of Pharmaceutical Chemistry , College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University , Dammam , Kingdom of Saudi Arabia.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):475-490. doi: 10.1080/21691401.2018.1561458.
Enhancement of CS-GA-PCL-NPs (Glycyrrhizic Acid-encapsulated-chitosan-coated-PCL-Nanoparticles) bioavailability in brain.
Double emulsification solvent evaporation method in order to develop CS-PCL-NPs (Chitosan-coated-PCL-Nanoparticles) followed by characterization of particle size and distribution, zeta potential, encapsulation efficiency and drug release (in vitro). To determine drug-uptake and its pharmacokinetic profile in brain as well as plasma, UHPLC (triple quadrupole Q-trap) MS/MS method was developed and optimized for CS-GA-PCL-NPs as well as to follow-up examined effective role of optimized NPs in reduction of all brain injury parameters after MCAO through the grip strength, locomotor activity, inflammatory cytokines levels, measurement of infarction volume and histopathological changes in neurons with safety/toxicity after i.n. in animals.
The developed NPs showed an average particle size, entrapment efficiency with PDI (polydispersity index) of 201.3 ± 4.6 nm, 77.94 ± 5.01% and 0.253 ± 0.019, respectively. Higher mucoadhesive property for CS-GA-PCL-NPs as compared to conventional and homogenized nanoformulations was observed whereas an elution time of 0.37 min and m/z of 821.49/113.41 for GA along with an elution time of 1.94 min and m/z of 363.45/121.40 was observed for hydrocortisone i.e. Internal standard (IS). Similarly, %CV i.e. inter and intra assay i.e. 0.49-4.41%, linear dynamic range (10-2000 ng/mL) and % accuracy of 90.00-99.09% was also observed. AUC with augmented C was noted (**p < .01), in Wistar rat brain as compared to i.v. treated group during pharmacokinetics studies. In MCA-occluded rats, enhanced neurobehavioral activity i.e. locomotor and grip strength along with a decrease in cytokines level (TNF-α and IL-1β) was observed, following i.n. administration.
CS-coated-GA-loaded-PCL-NPs when administered i.n. enhanced the bioavailability of the drug in rat brain as compared to i.v. administration. The observation from toxicity study concludes; the developed NPS are safe and free of any health associated risk.
提高 CS-GA-PCL-NPs（甘草酸包封壳聚糖包裹的 PCL-纳米颗粒）在脑部的生物利用度。
采用复乳溶剂蒸发法制备 CS-PCL-NPs（壳聚糖包裹的 PCL-纳米颗粒），并对其粒径及分布、Zeta 电位、包封率和体外药物释放进行表征。采用 UHPLC（三重四极杆 Q-阱）MS/MS 法测定 CS-GA-PCL-NPs 在脑和血浆中的药物摄取及其药代动力学特征，并通过握力、运动活性、炎性细胞因子水平、脑梗死体积测量和神经元组织病理学变化，以及鼻内给药后对 MCAO 后所有脑损伤参数的影响，来观察优化后的纳米颗粒的有效作用。
所制备的纳米颗粒平均粒径、包封效率和 PDI（多分散指数）分别为 201.3±4.6nm、77.94±5.01%和 0.253±0.019。与传统纳米制剂和均质纳米制剂相比，CS-GA-PCL-NPs 具有更高的黏膜黏附性，而 GA 的洗脱时间为 0.37min，m/z 为 821.49/113.41，氢化可的松即内标（IS）的洗脱时间为 1.94min，m/z 为 363.45/121.40。同样，还观察到 %CV（即批内和批间，0.49-4.41%）、线性动态范围（10-2000ng/mL）和 %准确度（90.00-99.09%）。在药代动力学研究中，与静脉注射治疗组相比，Wistar 大鼠脑内的 AUC 增加，C 增加（**p<0.01）。在 MCA 闭塞大鼠中，经鼻内给药后，观察到神经行为活动增强，即运动和握力增强，细胞因子水平（TNF-α和 IL-1β）降低。
与静脉给药相比，CS 包裹 GA 负载的 PCL-NPs 经鼻内给药可提高药物在大鼠脑内的生物利用度。毒性研究的结果表明，所开发的 NPS 是安全的，没有任何与健康相关的风险。
