The preparation and characteristics of sterically stabilized liposomes containing paclitaxel and super-paramagnetic iron oxide nanoparticles

Theranostics, combining therapy and diagnosis, is an appealing approach for chemotherapy. In the present study, we selected paclitaxel （PTX） as a therapeutic agent, super-paramagnetic iron oxide nanoparticles （SPIO） as a diagnostic agent and sterically stabilized liposomes as a carrier to prepare theranostic liposomes. The SPIO were prepared and characterized. Moreover, the sterically stabilized liposomes containing PTX and SPIO （PTX/SPIO-SSL） were prepared. The characteristics of PTX/SPIO-SSL were investigated. The results indicated that prepared SPIO exhibited super-paramagnetic and could be used for MRI. The average particle size of PTX/SPIO-SSL was about 170 rim, with a polydispersity index （PDI） less than 0.3. The zeta potential of PTX/SPIO-SSL was negative. The PTX entrapment efficiency of PTX/SPIO-SSL was more than 98%. The TEM results indicated the spherical structure and dense SPIO content in PTX/SPIO-SSL. The in vitro release of PTX from PTX/SPIO-SSL and PTX-SSL was almost identical at both pH 6.8 and 7.4. In conclusion, the PTX/SPIO-SSL were prepared and characterized in vitro. The anti-tumor and diagnostic activity of PTX/SPIO-SSL should be investigated deeply in future study.

Octreotide modified PEGylated liposomes improved the anticancer efficacy of doxorubicin in somatostatin receptor II positive tumor model

Active targeting drug delivery systems （TDDS）, which could improve drug therapeutic efficacy and reduce toxicity, are still the focus of many scientific researches in cancer therapy. The drug circulation time and tumor accumulation could be significantly increased with the application of sterically stabilized liposome （SSL）. SSL could also be modified easily with certain ligands to achieve targeting drug delivery. Because many tumors overexpress somatostatin receptors （SSTRs）, octreotide （OCT） becomes a potential targeting ligand due to its high affinity to SSTRs, especially to subtype 2 （SSTR2）. In this study, OCT was conjugated to methoxypolyethyleneglycol-distearoyl-phosphatidylethanolamine （DSPE-PEG2000）, and doxorubicin （DOX）-loaded SSL with a variable percentage of octreotide-methoxypolyethyleneglycol-distearoyl-phosphatidylethanolamine （DSPE-PEG/00o-OCT） were prepared （OCT-SSL-DOX）. All liposomes were about 90 nm in diameter and negatively charged on the surface, with DOX encapsulation efficiency at above 95%. OCT modification exhibited little effect on the physicochemical properties of SSL. In this study, cellular delivery efficacy of all prepared liposomes was evaluated in SSTIL2-positive cells in vitro by flow cytometry for the optimization of the OCT density on the surface of liposomes. Lipid formulation containing 1.5% DSPE-PEG20oo-OCT exhibited the highest efficiency of intracellular drug delivery. The modification of OCT did not alter the release behaviors of liposomal DOX in vitro, but OCT-SSL-DOX increased the cytotoxicity and improved the anti-tumor effect of liposomal DOX in SST1L2- positive cells and tumor-bearing mice models. In summary, OCT-modified SSL succeeded in increasing intracellular delivery and enhancing therapeutic efficacy of encapsulated anticancer agent, suggesting that it might be a promising TDDS for the treatment of SSTR2-overexpressing cancers.