الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
 |  | from | 23 |  |  |
| | | from | 23 | | |
Abstract
Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder associated with increased oxidative stress, the underlying vital process contributing to cell death. Tanshinone IIA (TAN) is a nutraceutical with a documented activity in treating many CNS disorders, particularly PD owing to its unique anti-inflammatory and antioxidant effect. However, its clinical utility is limited by its poor aqueous solubility, short half-life, and hence low concentration reaching targeted cells. This work aimed to develop a biocompatible chitosan coated nanostructured lipid carriers (CS-NLCs) for effective brain delivery of TAN for PD management. The proposed nanosystem was successfully prepared using a simple melt-emulsification ultra-sonication method, optimized and characterized both in vitro and in vivo in a rotenone-induced PD rat model. The developed TAN-loaded CS-NLCs (CS-TAN-NLCs) showed good colloidal properties (size ≤ 200 nm, PDI ≤ 0.2 and ζ-potential +20 mV), high drug-entrapment efficiency (> 97%) with sustained-release profile for 24 h. Following intranasal administration, CS-TAN-NLCs succeeded to achieve a remarkable antiparkinsonian and antidepressant effect in diseased animals compared to both the uncoated TAN-NLCs and free TAN suspension as evidenced by the conducted behavioral tests and improved histopathological findings. Furthermore, biochemical evaluation of oxidative stress along with inflammatory markers, nuclear factor- kabba