Abstract:
Targeting drugs to the central nervous system (CNS) is challenging due to the presence of the blood-brain barrier (BBB). The cutting edge in nanotechnology generates optimism to overcome the growing challenges in biomedical sciences through the effective engineering of nanogels. The primary objective of the present report was to develop and characterize a biocompatible natural chitosan (CS)-based NG that can be tracked thanks to the tricarbocyanine (CNN) fluorescent probe addition on the biopolymer backbone. FTIR shed light on the chemical groups involved in the CS and CNN interactions and between CNN-CS and tripolyphosphate, the cross-linking agent. Both in vitro and in vivo experiments were carried out to determine if CS-NGs can be utilized as therapeutic delivery vehicles directed towards the brain. An ionic gelation method was chosen to generate cationic CNN-CS-NG. DLS and TEM confirmed that these entities\' sizes fell into the nanoscale. CNN-CS-NG was found to be non-cytotoxic, as determined in the SH-SY5Y neuroblastoma cell line through biocompatibility assays. After cellular internalization, the occurrence of an endo-lysosomal escape (a crucial event for an efficient drug delivery) of CNN-CS-NG was detected. Furthermore, CNN-CS-NG administered intraperitoneally to female CF-1 mice were detected in different brain regions after 2 h of administration, using fluorescence microscopy. To conclude, the obtained findings in the present report can be useful in the field of neuro-nanomedicine when designing drug vehicles with the purpose of delivering drugs to the CNS.
摘要:
由于血脑屏障(BBB)的存在,将药物靶向中枢神经系统(CNS)具有挑战性。纳米技术的前沿使人们乐观地通过有效的纳米凝胶工程来克服生物医学科学中日益增长的挑战。本报告的主要目的是开发和表征生物相容性的基于天然壳聚糖(CS)的NG,该NG可以通过在生物聚合物主链上添加三碳花青(CNN)荧光探针进行跟踪。FTIR揭示了CS和CNN相互作用以及CNN-CS和三聚磷酸盐之间的化学基团,交联剂。进行体外和体内实验以确定CS-NG是否可用作指向脑的治疗性递送载体。选择离子凝胶化方法以产生阳离子CNN-CS-NG。DLS和TEM证实这些实体的尺寸落入纳米级。CNN-CS-NG被发现是非细胞毒性的,通过生物相容性测定在SH-SY5Y神经母细胞瘤细胞系中测定。细胞内化后,检测到CNN-CS-NG的内-溶酶体逃逸(有效药物递送的关键事件)的发生.此外,给药2h后,对雌性CF-1小鼠腹膜内给药的CNN-CS-NG在不同的脑区检测到,使用荧光显微镜。最后,本报告中获得的发现在设计旨在将药物递送至CNS的药物载体时,可用于神经纳米医学领域。