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  • Title: The targeting of surface modified silica nanoparticles to inflamed tissue in experimental colitis.
    Author: Moulari B, Pertuit D, Pellequer Y, Lamprecht A.
    Journal: Biomaterials; 2008 Dec; 29(34):4554-60. PubMed ID: 18790531.
    Abstract:
    One aspect in the emerging field of nanomedicine is site specific drug delivery via nanoparticles. The use of nanoparticles allows for increased therapeutic efficiency with a lowered risk for and extent of adverse reactions resulting from systemic drug absorption. 5-Amino salicylic acid (5ASA) loaded silica nanoparticles (SiNP) are proposed here as drug delivery system for specific accumulation in inflamed colonic tissues allowing for selective medication delivery to such inflammation sites. The drug was covalently bound to SiNP by a four-step reaction process. In-vitro toxicity of modified SiNP was tested in appropriate cell culture systems, while targeting index and therapeutic efficiency were evaluated in a pre-existing colitis in mice. Particle diameter was around 140 nm after final surface modification. In-vitro drug release demonstrated significant drug retention inside the NP formulation. Toxicity of the different formulations was evaluated in-vitro cell culture exhibiting a lowered toxicity for 5ASA when bound to SiNP. In-vivo, oral SiNP were found to accumulate selectively in the inflamed tissues allowing for significant amounts of drug load. SiNP demonstrated their therapeutic potential by significantly lowering the therapeutically necessary drug dose when evaluating clinical activity score and myeloperoxidase activity (untreated control: 28.0+/-5.0 U/mg; 5ASA-solution (100mg/kg): 8.2+/-3.4 U/mg 5ASA-SiNP (25mg/kg): 5.2+/-2.4 U/mg). SiNP allow to combine advantages from selective drug targeting and prodrugs appearing to be a promising therapeutic approach for clinical testing in the therapy of inflammatory bowel disease.
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