C Oussoren1, G Storm. 1. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, The Netherlands.
Abstract
PURPOSE: The aim of the present paper was to assess the effect of inclusion of distearoylphosphatidylethanolamine-poly(ethyleneglycol) (DSPE-PEG) into liposomal bilayers on the lymphatic uptake and lymph node localization of liposomes after subcutaneous administration. METHODS: [3H]-Cholesteryloleylether labeled liposomes of various composition and sizes were injected s.c. into the dorsal side of the foot of rats. At several time-points after injection, blood levels of liposomes were determined. Lymphatic uptake from the s.c. site of injection and lymph node localization in regional lymph nodes were determined at the end of the 52 h observation period. RESULTS: The results demonstrate that inclusion of DSPE-PEG into several types of liposomes has only a modest effect on lymphatic uptake. Also lymph node localization is only slightly affected by PEG-mediated steric stabilization. CONCLUSIONS: Factors other than the presence of a steric barrier are more important in determining lymphatic uptake from the s.c. injection site. The observation that lymph node localization was only slightly affected by PEG-coating strongly suggests that macrophage uptake is not the only important mechanism of lymph node localization of s.c. administered liposomes.
PURPOSE: The aim of the present paper was to assess the effect of inclusion of distearoylphosphatidylethanolamine-poly(ethyleneglycol) (DSPE-PEG) into liposomal bilayers on the lymphatic uptake and lymph node localization of liposomes after subcutaneous administration. METHODS: [3H]-Cholesteryloleylether labeled liposomes of various composition and sizes were injected s.c. into the dorsal side of the foot of rats. At several time-points after injection, blood levels of liposomes were determined. Lymphatic uptake from the s.c. site of injection and lymph node localization in regional lymph nodes were determined at the end of the 52 h observation period. RESULTS: The results demonstrate that inclusion of DSPE-PEG into several types of liposomes has only a modest effect on lymphatic uptake. Also lymph node localization is only slightly affected by PEG-mediated steric stabilization. CONCLUSIONS: Factors other than the presence of a steric barrier are more important in determining lymphatic uptake from the s.c. injection site. The observation that lymph node localization was only slightly affected by PEG-coating strongly suggests that macrophage uptake is not the only important mechanism of lymph node localization of s.c. administered liposomes.
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