The objective of the present work was to investigate the optimum density of octreotide on the surface of nanostructured lipid carriers (NLC) loaded with hydroxycamptothencine (HCPT) to enhance receptor-mediated endocytosis and tumor targeting selectivity. Different amounts of octreotide-polyethylene glycol (100) monostearate (OPMS), a ligand for somatostatin receptors (SSTRs), were coupled into NLC. In vitro evaluation of OPMS modified NLCs (O-NLCs) was done by studying the physicochemical properties, drug release, cellular uptake and cytotoxicity. Whereas in vivo evaluation was done by studying the tissue distribution in S180 tumor-bearing mice through ex vivo fluorescence imaging and HCPT quantitative study. The results showed that O-NLCs with an average size of ∼100 nm possessed obvious sustained release. When OPMS was used in the amount of 5 μmol (O₅-NLC) highest cellular uptake, cytotoxicity in SMMC-7721 cell line and remarkable accumulation in S180 tumor were observed. The treatments of O₅-NLC brought about significant tumor inhibition and prolonged the median survival time as compared with HCPT, unmodified NLC and the pegylated NLC (P₅-NLC) groups. It appears that to achieve a more rational approach of receptor mediated tumor targeted drug delivery system the surface density of the targeting moiety on the surface of nanocarriers should be considered.
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