Sirolimus encapsulated liposomes for cancer therapy : physicochemical and mechanical characterization of sirolimus distribution within liposome bilayers

Onyesome, Ichioma and Lamprou, Dimitrios and Sygellou, Lamprini and Owusu-Ware, Samuel and Antonijevic, Milan and Chowdhry, Babur and Douroumis, D. (2013) Sirolimus encapsulated liposomes for cancer therapy : physicochemical and mechanical characterization of sirolimus distribution within liposome bilayers. Molecular Pharmaceutics, 10 (11). pp. 4281-4293. ISSN 1543-8384

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Abstract

Sirolimus has recently been introduced as a therapeutic agent for breast and prostate cancer. In the current study, conventional and Stealth® liposomes were used as carriers for the encapsulation of sirolimus. The physicochemical characteristics of the sirolimus liposome nanoparticles were investigated including the particle size, zeta potential, stability and membrane integrity. In addition atomic force microscopy was used to study the morphology, surface roughness and mechanical properties such as elastic modulus deformation and deformation. Sirolimus encapsulation in Stealth liposomes® showed a high degree of deformation and lower packing density especially for dipalmitoyl-phosphatidylcholine (DPPC) Stealth® liposomes compared to unloaded. Similar results were obtained by differential scanning calorimetry (DSC) studies; sirolimus loaded liposomes were found to result in a distorted state of the bilayer. X-ray photon electron (XPS) analysis revealed a uniform distribution of sirolimus in multilamellar DPPC Stealth® liposomes compared to a non-uniform, greater outer layer lamellar distribution in distearoylphosphatidylcholine (DSPC) Stealth® liposomes.