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  • Title: New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin.
    Author: Garcia-Fuentes M, Torres D, Alonso MJ.
    Journal: Int J Pharm; 2005 May 30; 296(1-2):122-32. PubMed ID: 15885464.
    Abstract:
    The aim of the present work was to develop a new nanoparticulate system, consisting of lipid nanoparticles coated with chitosan (CS), intended for the oral administration of peptide drugs. These new nanoparticles were studied, and compared with the previously developed PEG-coated lipid nanoparticles, with regard to their ability to incorporate and deliver the model peptide salmon calcitonin (sCT). Moreover, the influence of the core composition, either a solid triglyceride (tripalmitin), or a mixture of a liquid and a solid triglyceride (Miglyol 812 and tripalmitin) on the encapsulation and release of sCT was investigated. The results showed that a CS coating could be formed around the tripalmitin nanoparticles by simple incubation of the lipid cores in a CS solution, due to the high affinity of CS for the lipid core. In addition, sCT could be efficiently associated, irrespective of the core composition, to the nanoparticles. This important association was attributed to the marked affinity of sCT for the lipid cores, as confirmed by the adsorption studies. However, the nature of the coating affected the surface association of the peptide, which was less important for the nanoparticles coated with CS, than for PEG-coated nanoparticles. This was attributed to the displacement of the sCT molecules located on the surface of the nanoparticles by the positively charged CS molecules. This reduced surface association led to a decrease in the burst release effect, which was more pronounced for the nanoparticles coated with PEG than for those coated with CS. Following the initial burst, the systems provided a continuous and slow release of the associated peptide, independently of the nature of the coating. This slow release was attributed to the affinity of the peptide for the lipids and to the absence of degradation of the lipid matrix under the in vitro release conditions.
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