Effect of octreotide surface density on receptor-mediated endocytosis in vitro and anticancer efficacy of modified nanocarrier in vivo after optimization.

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.