Encapsulation and\nStabilization of α‑Lipoic\nAcid in Cyclodextrin Inclusion Complex Electrospun Nanofibers: Antioxidant\nand Fast-Dissolving α‑Lipoic Acid/Cyclodextrin Nanofibrous\nWebs

Abstract

In this study, electrospinning of nanofibers from alpha-lipoic\nacid/cyclodextrin inclusion complex systems was successfully performed\nwithout having any polymeric matrix. Alpha-lipoic acid (α-LA)\nis a natural antioxidant compound which is widely used as a food supplement.\nHowever, it has limited water solubility and poor thermal and oxidative\nstability. Nevertheless, it is possible to enhance its water solubility\nand thermal stability by inclusion complexation with cyclodextrins.\nHere, hydroxypropyl-beta-cyclodextrin (HP-β-CyD) and hydroxypropyl-gamma-cyclodextrin\n(HP-γ-CyD) were chosen as host molecules for forming inclusion\ncomplexation with α-LA. Accordingly, α-LA was inclusion\ncomplexed with HP-β-CyD and HP-γ-CyD by using very high\nconcentrated aqueous solutions of CyD (200%, w/v) having 1/1 and 2/1\nmolar ratio of α-LA/CyD. Except α-LA/HP-β-CyD (1/1)\nsolution, other α-LA/CyD solutions were turbid indicating the\npresence of some noncomplexed α-LA whereas α-LA/HP-β-CyD\n(1/1) solution was very homogeneous signifying that α-LA was\nfully complexed with HP-β-CyD. Even so, electrospinning was\nperformed for all of the α-LA/HP-β-CyD (1/1 and 2/1) and\nα-LA/HP-γ-CyD (1/1 and 2/1) aqueous solutions, and defect-free\nbead-less and uniform nanofibers were successfully obtained for all\nof the α-LA/CyD solutions. However, the electrospinning process\nfor α-LA/CyD (1/1) systems was much more efficient than the\nα-LA/CyD (2/1) systems, and we were able to produce self-standing\nand flexible nanofibrous webs from α-LA/CyD (1/1) systems. α-LA\nwas efficiently preserved during the electrospinning process of α-LA/CyD\n(1/1) systems and the resulting electrospun α-LA/HP-β-CyD\nand α-LA/HP-γ-CyD nanofibers were produced with the molar\nratios of ∼1/1 and ∼0.85/1 (α-LA/CyD), respectively.\nThe better encapsulation efficiency of α-LA in α-LA/HP-β-CyD\nnanofibers was due to higher solubility increase and higher binding\nstrength between α-LA and HP-β-CyD as revealed by the\nphase solubility test. α-LA was in the amorphous state in α-LA/CyD\nnanofibers and both α-LA/HP-β-CyD and α-LA/HP-γ-CyD\nnanofibers were dissolved very quickly in water and also when they\nwetted with artificial saliva. Additionally, the antioxidant activity\nof pure α-LA and α-LA/CyD nanofibers was comparatively\nevaluated using ABTS radical cation assay. α-LA/CyD nanofibers\nhave shown significantly higher antioxidant performance compared to\npure α-LA owing to improved water solubility by CyD inclusion\ncomplexation. The thermal stability enhancement of α-LA in α-LA/CyD\nnanofibers was achieved compared to pure α-LA under heat treatment\n(100 °C for 24 h). These promising results support that antioxidant\nα-LA/CyD nanofibers may have potential applications as orally\nfast-dissolving food supplements.