Cyclodextrin-based siRNA delivery nanocarriers: a state-of-the-art review

Authors: Chaturvedi, Kiran1; Ganguly, Kuntal1; Kulkarni, Anandrao R1; Kulkarni, Venkatarao H1; Nadagouda, Mallikarjuna N1; Rudzinski, Walter E2; Aminabhavi, Tejraj M1

Source: Expert Opinion on Drug Delivery, Volume 8, Number 11, November 2011 , pp. 1455-1468(14)

Publisher: Informa Healthcare

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Abstract:

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords: cyclodextrin; nanocarriers; non-viral vector; siRNA; targeted delivery

Document Type: Research Article

DOI: http://dx.doi.org/10.1517/17425247.2011.610790

Affiliations: 1: 1 SET's College of Pharmacy, Department of Pharmacology, Dharwad 580 002, India ++91 836 2778279; ++91 836 2467190;, Email: aminabhavi@yahoo.com 2: 3 Texas State University, Department of Chemistry, San Marcos, TX 78666, USA

Publication date: November 1, 2011

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