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KMID : 0369820160460040393
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Jorunal of Korean Pharmaceutical Sciences
2016 Volume.46 No. 4 p.393 ~ p.402
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Current advances in developing cationic lipid-based nanoparticles as a vehicle for improving adenoviral gene delivery
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Kim Soo-Yeon
Lee Mi-Kyung
Lim Soo-Jeong
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Abstract
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Preclinical and early clinical studies of the adenovirus-based vectors for gene therapy have shown considerable promise for the future. Use of adenoviral vectors in gene therapy is, however, limited by the lack of adenoviral receptors on targeted cell types, induction of neutralizing antibodies, short blood circulation half-life of adenovirus (Ad), hepatotoxicity and low selective accumulation in the target disease site. Researchers have shown that chemical modification of the Ad surface may be an effective means to overcome the current limitations of Ad-mediated gene transfer. In comparison, a small number of studies have addressed these issues by developing cationic lipid-based nanoparticles as an Ad-complexing formulation. Findings from these studies indicate that Ad complexation with cationic lipid-based nanoparticles is an effective and simple means to overcome the lack of receptors in target cells in vitro and to reduce the immunogenicity and hepatotoxicity of Ad vectors in vivo. In contrast, findings about the effect of cationic nanoparticle complexation in increasing the Ad accumulation in the target site in vivo are not consistent among studies. A definitive conclusion cannot be drawn at the current state due to the limited number of studies but the reasons for the discrepancy may include the differences in the lipid composition and the structure of cationic lipid-based nanoparticles. This review gives a comprehensive overview of current status in the development of cationic lipid-based nanoparticles as a vehicle to overcome the challenges of adenoviral vectors.
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KEYWORD
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Cationic lipid, Nanoparticles, Adenovirus, Gene delivery, Liposomes
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