Polycationic Amphiphilic Cyclodextrin-Based Nanoparticles for Therapeutic Gene Delivery

Abstract

Aim: In this study, a set of polycationic amphiphilic cyclodextrins featuring self-assembling capabilities in the presence of nucleic acids have been evaluated as therapeutic gene vectors for in vivo purposes. Materials & Methods: A tetradecacationic structure incorporating 14 primary amino groups and 7 thioureido groups in the primary face of the cyclooligosaccharide core and 14 hexanoyl chains in the secondary face was judged to be optimal for therapeutic gene delivery. Results & Conclusion: This compound efficiently mediated serum-resistant transfection in HeLa and HepG2 cells, comparing favorably with branched poly(ethyleneimine), with a low associated toxicity. Further transfection experiments using an encoding therapeutic gene plasmid (pCMVIL-12) were effected to report expression levels of IL-12. Finally, in vivo gene delivery experiments by systemic injection in mice indicated relatively high transfection levels in the liver, overcoming trapping of the nanoparticles in lung cells, with low toxicity.

Cyclodextrin-based multivalent glycodisplays: covalent and supramolecular conjugates to assess carbohydrate–protein interactions

“…The increasing awareness of the potential of polycationic CD derivatives in the design of nonviral gene delivery systems has led several groups to explore the suitability of polycationic CD conjugates to impart, simultaneously, stability and targeting capabilities of the corresponding complexes with plasmid DNA (pDNA), for which the term CDplexes has been coined. [148][149][150][151][152][153][154][155][156][157] Uekama, Arima and co-workers conceived a series of multifunctional CD conjugates consisting of a poly(amidoamine) (PAMAM) starburst dendrimer 102 onto which one-to-two aCD units (103) were randomly attached through a single primary (C-6) position by reaction with the corresponding 6 Itosyl derivative 103. Some of the remaining primary amino groups of the dendrimer were subsequently engaged in thiourea forming reactions with isothiocyanate-armed aMan (104) and aGal derivatives to afford the corresponding polycationic aCD-PAMAM glycoconjugates.…”

Click-Modified Cyclodextrins as Nonviral Vectors for Neuronal siRNA Delivery

“…14 The potential of CDs as delivery agents for therapeutic oligonucleotides is well established. 15,16 Chemical modification of CDs has yielded monodisperse nonviral gene delivery vectors. 17−21 Modifications of the basic β-CD structure, including introduction of cationic and/or amphiphilic moieties have resulted in a group of novel vectors which can complex pDNA and efficiently deliver it to various in vitro cell culture models, including liver (Hep G2) cells 22,23 and undifferentiated and differentiated intestinal epithelial (Caco2) cells.…”

Cyclodextrin nanoassemblies: a promising tool for drug delivery

“…Moreover, it is important to keep in mind the application when designing NPs. For example, grafted long chains (C 12 -C 16 …”

“…Many interesting reviews have been published on cationic amphiphilic CDs for gene delivery, for example [15][16][17], whereas only a few anionic amphiphilic CDs have been studied for their self-assembly properties [18,19]. In this overview, our purpose is to provide a state-of-the-art of the supramolecular assemblies of nonionic amphiphilic CDs and their physicochemical characteristics, which are crucial for drug delivery (Table 1).…”