Chitosan-coated nanostructured lipid carriers for effective brain delivery of Tanshinone IIA in Parkinson’s disease: interplay between nuclear factor-kappa β and cathepsin B
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 phytomedicine 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) and 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 β (NF-Kβ) and cathepsin B further confirmed the potential of the CS-TAN-NLCs in enhancing brain delivery and hence the therapeutic effect of TAN of treatment of PD. Accordingly, CS-TAN-NLCs could be addressed as a promising nano-platform for the effective management of PD.
Materials
Tanshinone IIA (purity 98%) was purchased from Baoji Guokang Bio-Technology Co., Ltd, China. Labrafac™ lipophile WL 1349, Labrafac™ PG, Peceol™, Compritol® 888 ATO, Precirol® ATO 5, and Glyceryl monostearate were kindly gifted by Gattefossé S.A., Saint-Priest, France. Kolliphor® HS15 and low molecular weight chitosan were obtained from Sigma-Aldrich, USA. Tween® 80 and absolute ethanol were purchased from ADWIC, El-Nasr Pharmaceutical Chemicals Co., Cairo, Egypt. All other chemicals and organic solvents were of analytical grade.
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Hassan, D.M., El-Kamel, A.H., Allam, E.A. et al. Chitosan-coated nanostructured lipid carriers for effective brain delivery of Tanshinone IIA in Parkinson’s disease: interplay between nuclear factor-kappa β and cathepsin B. Drug Deliv. and Transl. Res. (2023).
https://doi.org/10.1007/s13346-023-01407-7