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.

Exploring versatile applications of cyclodextrins: an overview

“…Their activity as linking agent was confirmed when cross-linking of PEI was done by Huang et al using 2-HP-b-CD and 2-HP-g-CD. The two resultant polymers were better in properties as they showed lower cytotoxicity than PEI 25 kDa, with transfection efficiency in SKOV-3 cells approximately 20 and two times greater than that obtained by PEI 600Da and PEI 25 kDa, respectively (Lai, 2014).…”

“…This can be well exemplified by CD derivatives polycationic amphiphilic CDs (paCDs; built by the change in the facial anisotropy of the truncated-cone CD by the introducing cationic and hydrophobic elements). By controlling the various molecular parameters such as charge density, hydrophilic-hydrophobic balance, nature of the functional groups and spacer length, the complexing of DNA with CDs can be improved finally, regulating the transfection efficiency of paCDs (Lai, 2014). CDs also have an important role in linking various polymers through covalent linkage forming large molecular structures similar to gene carriers, thereby behaving as a linking agent.…”

“…The role of CD as threading agent can be better explained by the experiments conducted by Li's group, who have produced large number of supramolecular polyrotaxanes, which comprise of cationic a-CD rings threaded and blocked on a poly [(ethylene oxide)-ran-(propylene oxide)] [P (EO-r-PO)] random copolymer. The function of CDs as pendants can be explained by taking the example of vectors produced by this method is the polyamidoamine (PAMAM) dendrimer conjugates with all the three parent CDs (Lai, 2014). Some of the applications of CD in non-viral gene delivery are given in Table 14.…”

A family of cationic polyamides for in vitro and in vivo gene transfection

“…However, for successful gene therapy, the availability of low-toxic and highly efficient gene delivery vectors remains a huge challenge [2]. Over the past two decades, much effort has been made to develop functionalized cationic polymers as non-viral gene delivery vectors [3]. Compared to potent viral vectors [4], cationic polymers gain additional advantages including low immunogenicity, non-oncogenicity, relatively high gene-carrying capacity, large-scale production and low cost.…”

Gd(III) ion-chelated supramolecular assemblies composed of PGMA-based polycations for effective biomedical applications

“…20 In particular, cyclodextrins (CDs) and their derivatives have been widely utilized for constructing supramolecular gene delivery systems, mainly because of their superior biocompatibility. [21][22][23] With the host-guest interaction strategy, we successfully prepared one PGEA-based supramolecular delivery system by tying multiple β-cyclodextrin (β-CD)-cored star PGEA polymers to an adamantine-modified linear PGEA backbone. 24 Such PGEA supramolecules markedly increased transfection efficiencies.…”