Polysaccharides as Nanomaterials for Therapeutics - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 142

5.4.5 Cyclodextrin-BasedNanoparticles
Amphiphilic cyclodextrins have been widely used for the preparation
of nanoparticles for drug delivery. This can be attributed to the
outstanding drug-loading efficiencies of amphiphilic cyclodextrin-
based nanoparticles that do not require the presence of surfactant
in the preparation [121]. In addition, nanoparticles can be prepared
directly from pre-formed inclusion complexes of drug with
amphiphilic cyclodextrins, which ensures both high drug loading
and delayed burst eff ect [121]. Interestingly, the first experimental
therapeutic to provide targeted delivery of siRNA in humans utilized
a cyclodextrin-based nanoparticle [122].
Choisnard et al. prepared self-assembled nanoparticles of
decanoate β-cyclodextrin esters and hexanoate β-cyclodextrin esters
[123]. The mean size and polydispersity were significantly aff ected
by the nature of solvent used in the nano-precipitation technique. In
addition, the globular shape of nanoparticle was determined by the
hydrophobic moiety used for modification [123].
Cyclodextrin-containing polymers have demonstrated unique
capabilities for nucleic acid delivery: They have demonstrated
low in vitro and in vivo toxicities when compared with other
non-cyclodextrin-containing polycations such as poly-L-lysine
and polyethylenimine. In addition, these polycations form self-
assembled nanoparticles with oligonucleotides [124]. These
advantages have been utilized for the preparation of the first
clinically tested nanoparticle for siRNA delivery, which is composed
of cyclodextrin-containing polycation, a polythethylene glycol (PEG)
steric stabilization agent, and human transferrin as a targeting
ligand [122]. Structurally, the cyclodextrin-containing polycation
assembles with the siRNA primarily via electrostatic interactions.
It condenses siRNA and protects it from nuclease degradation. The
cyclodextrins within the polymer chains that reside on the surface of
the nanoparticles are used for assembling PEG, which is conjugated
to adamantine. The assembly of PEG-adamantine is due to inclusion
complex formation between the adamantine and cyclodextrin. The
same principle is applied for the assembly of the targeting ligand
transferrin, which was chosen since its receptor is upregulated on
cancer cells. Primary results from phase I clinical trials using RRM2
siRNA-containing nanoparticles have been recently published
[125]. Following systemic administration to patients with solid