Cyclodextrins in non-viral gene delivery

Abstract

Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides. They consist of (α-1,4)-linked glucose units, and possess a basket-shaped topology with an "inner-outer" amphiphilic character. Over the years, substantial efforts have been undertaken to investigate the possible use of CDs in drug delivery and controlled drug release, yet the potential of CDs in gene delivery has received comparatively less discussion in the literature. In this article, we will first discuss the properties of CDs for gene delivery, followed by a synopsis of the use of CDs in development and modification of non-viral gene carriers. Finally, areas that are noteworthy in CD-based gene delivery will be highlighted for future research. Due to the application prospects of CDs, it is anticipated that CDs will continue to emerge as an important tool for vector development, and will play significant roles in facilitating non-viral gene delivery in the forthcoming decades.

Keywords: Cyclodextrin; Gene delivery; Non-viral vector; Polymer; Transfection.

Fig. 1

The structures and space-filling models of (i) α-CD, (ii) β-CD and (iii) γ-CD. In the space-filling models, hydrogen, carbon and oxygen atoms are colored in black, white and gray, respectively.

Fig. 2

Structures of some derivatives of CDs. These derivatives include (i) heptakis(6-amino-6-deoxy)-β-CD, (ii) heptakis(6-deoxy-6-methoxyethylamino)-β-CD, (iii) heptakis[2,3-di-O-acetyl-6-deoxy-6-(1-methyl-1H-imidazol-2-yl)]-β-CD, (iv) heptakis(6-deoxy-6-pyrid-4-ylamino)-β-CD, (v) heptakis(2,3-di-O-acetyl-6-deoxy-6-pyrid-4-ylamino)-β-CD, (vi) heptakis[6-(1-n-butyl-1H-imidazol-2-yl)-6-deoxy]-β-CD, and (vii) heptakis[2,3-di-O-acetyl-6-(1-n-butyl-1H-imidazol-2-yl)-6-deoxy]-β-CD.

Fig. 3

Major approaches of employing CDs for applications in gene delivery. The arrows drawn with a broken line indicate that derivatives of CDs have not only been investigated as gene carriers, but have also been used as linking agents or structural modifiers.

Fig. 4

Performance of TAT-PEI-β-CD in gene delivery to PMSCs. (A) Time course study of the transfection efficiency of TAT-PEI-β-CD and PEI-β-CD in PMSCs. (B) MTT assay in PMSCs after treatment with PEI 25 kDa, PEI 0.8 kDa, PEI-β-CD and TAT-PEI-β-CD. (Adapted from Ref.with kind permission from Springer Science + Business Media B.V.).