Abstract

Purpose: Free radicals such as hydroxyl and peroxide are contributing factors to neuronal destruction in cerebral ischemia. Alpha-lipoic acid (ALA) is one of the potent known antioxidants. Preparation of ALA niosomes allows IV injection and can increase bioavailability and penetration into the central nervous system (CNS). Methods: Film hydration method was used to prepare different niosomes composed of Span®, Tween®, and cholesterol at different molar ratio. ALA and niosome-forming compounds were dissolved in chloroform, before removing the organic solvent by rotary evaporator. Animals were randomly divided into four groups: Sham, control group, intravenous (IV) injection of empty niosomes plus intraperitoneal (IP) injection of ALA solution, and finally, IV injection of ALA niosomes. Rats were subjected to deep anesthesia before inducing cerebral ischemia, then, their internal common carotid arteries were clamped for 15 min and reperfusion was done for 30 min. Niosomal ALA was injected intravenously just before declamping. Results: Mean volume diameter of the prepared niosomes was between 4.36 ± 0.82 and 19.95 ± 1.21 μm in different formulations. Encapsulation efficiency percent (EE%) of ALA in the selected formulation, Span60/Tween60/cholesterol (35:35:30 molar ratio), was 94.5 ± 0.2, and 59.27 ± 5.61% of ALA was released after 4h. In the niosomal group, the rate of reduction in complications of cerebral ischemia such as histopathologic changes and acute damage (from score 3 to 1) in CNS was higher than other groups. Conclusion: The obtained results show that niosomes can be used as effective drug delivery systems for ALA in cerebral ischemia.

Highlights

  • Cerebral ischemia is one of the major causes of mortality worldwide

  • Encapsulation efficiency percent (EE%) of Alpha-lipoic acid (ALA) in the selected formulation, Span60/Tween60/Cholesterol (35:35:30 molar ratio), was 94.5 ± 0.2, and 59.27 ± 5.61% of ALA was released after 4h

  • The rate of reduction in complications of cerebral ischemia such as histopathologic changes and acute damage in central nervous system (CNS) was higher than other groups

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Summary

Results

Mean volume diameter of the prepared niosomes was between 4.36 ± 0.82 and 19.95 ± 1.21. Encapsulation efficiency percent (EE%) of ALA in the selected formulation, Span60/Tween60/Cholesterol (35:35:30 molar ratio), was 94.5 ± 0.2, and 59.27 ± 5.61% of ALA was released after 4h. The rate of reduction in complications of cerebral ischemia such as histopathologic changes and acute damage (from score 3 to 1) in CNS was higher than other groups. Conclusion: The obtained results show that niosomes can be used as effective drug delivery systems for ALA in cerebral ischemia

Introduction
Materials and Methods
Name Constituents of lipid phase Molar ratio
All neurons affected
Full Text
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