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Serum-stable, long-circulating paclitaxel-loaded colloidal carriers decorated with a new amphiphilic PEG derivative
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The paper describes sterically stabilized lipid nanocapsules (LNC) and multilamellar liposomes (MLV) coated using a new amphiphilic conjugate of PEG2000 with a 2-alkyl-lipoamino acid (LAA). A complement activation assay (CH50) and uptake experiments by THP-1 macrophage cells were used to assess in vitro the effectiveness of the PEG-LAA derivative of modifying the surface behavior of nanocarriers. Administered to rats or Swiss mice, respectively, the PEG2000-LAA—modified LNC and MLV showed plasma half-lives longer than the corresponding naked carriers.
To assess the ability of nanocarriers to specifically reach tumor sites, paclitaxel (PTX)—loaded LNC and MLV were administered subcutaneously to rats implanted with a 9L glioma. Animals treated with saline or naked LNC and MLV underwent a quick expansion of tumor mass, up to a volume of 2000 mm3 25 days after the injection of tumor cells. On the contrary, treatment with a PEG-LAA modified LNC carrier reduced the growth of the tumor volume, which did not exceed 1000 mm3 by day 25. Analogous positive results were obtained with the liposomal systems. The experimental findings confirmed that these new PEG-LAA conjugates allow to obtain sterically stable nanocarriers that behave effectively and in a comparable or even better way than the (phospho)lipid PEG derivatives commercially available.
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