title: In vivo sustained release of siRNA from solid lipid nanoparticles.
abstract: Small interfering RNA (siRNA) is a highly potent drug in gene-based therapy with a challenge of being delivered in a sustained manner. Nanoparticle drug delivery systems allow for incorporating and controlled release of therapeutic payloads. We demonstrate that solid lipid nanoparticles can incorporate and provide sustained release of siRNA. Tristearin solid lipid nanoparticles, made by nanoprecipitation, were loaded with siRNA (4.4-5.5 wt % loading ratio) using a hydrophobic ion pairing approach that employs the cationic lipid DOTAP. Intradermal injection of these nanocarriers in mouse footpads resulted in prolonged siRNA release over a period of 10-13 days. In vitro cell studies showed that the released siRNA retained its activity. Nanoparticles developed in this study offer an alternative approach to polymeric nanoparticles for encapsulation and sustained delivery of siRNA with the advantage of being prepared from physiologically well-tolerated materials.
authors.affiliation: Department of Chemistry, Stanford University, 333 Campus Drive, Stanford, California 94305-5080, United States.
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Lobovkina
authors.forename: Gunilla B
authors.initials: GB
authors.lastname: Jacobson
authors.forename: Emilio
authors.initials: E
authors.lastname: Gonzalez-Gonzalez
authors.forename: Robyn P
authors.initials: RP
authors.lastname: Hickerson
authors.forename: Devin
authors.initials: D
authors.lastname: Leake
authors.forename: Roger L
authors.initials: RL
authors.lastname: Kaspar
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
authors.forename: Richard N
authors.initials: RN
authors.lastname: Zare
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004058:Diffusion; D020868:Gene Silencing; D008422:Materials Testing; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry*; D014280:Triglycerides / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D053769:Nanocapsules; D034741:RNA, Small Interfering; D014280:Triglycerides; C022618:tristearin
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