title: Cyclodextrin-based siRNA delivery nanocarriers: a state-of-the-art review.
abstract: BACKGROUND
  The discovery of synthetic small interfering RNA (siRNA) has led to a surge of interest in harnessing RNA interference (RNAi) technology for biomedical applications and drug development. Even though siRNA can be a powerful therapeutic drug, its delivery remains a major challenge, due to the difficulty in its cellular uptake. Naked siRNA has a biological half-life of less than an hour in human plasma. To increase the lifetime and improve its therapeutic efficacy, non-viral vectors have been developed. As a natural evolution, cyclodextrins (CDs), which are natural cyclic oligosaccharides, have recently been applied as delivery vehicles for siRNA, and this in turn, has led to a surge of interest in this area.
  
  
  METHODS
  This review discusses the recent advances made in the design of delivery strategies for siRNA, focusing on CD-based delivery vectors, because these have demonstrated clinical success. The methods of preparation of CD-based vectors, their characterization, transfection efficiencies, cellular toxicity, preclinical and clinical trials are also addressed, as well as future therapeutic applications.
  
  
  CONCLUSIONS
  siRNA-mediated RNAi therapeutics is beginning to transform healthcare, particularly, for the treatment of solid tumors. For example, CALAA01, a targeted, self-assembling nanoparticle system based on CD complexed with siRNA has been effective in phase I clinical trials. Although siRNA therapeutics suffers from problems related to off-target effects and non-specific gene silencing, these problems can be overcome by reducing the nanoparticle size, improving the targeting efficiency and by modifying the primary sequence of the siRNA.
authors.affiliation: SET's College of Pharmacy, Department of Pharmacology, Dharwad, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Chaturvedi
authors.forename: Kuntal
authors.initials: K
authors.lastname: Ganguly
authors.forename: Anandrao R
authors.initials: AR
authors.lastname: Kulkarni
authors.forename: Venkatarao H
authors.initials: VH
authors.lastname: Kulkarni
authors.forename: Mallikarjuna N
authors.initials: MN
authors.lastname: Nadagouda
authors.forename: Walter E
authors.initials: WE
authors.lastname: Rudzinski
authors.forename: Tejraj M
authors.initials: TM
authors.lastname: Aminabhavi
mesh_terms: D000818:Animals; D003505:Cyclodextrins / Q000737:chemistry*; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D006801:Humans; D049329:Nanostructures / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D003505:Cyclodextrins; D034741:RNA, Small Interfering