Enhanced Ehrlich tumor inhibition using DOX-NP and gold nanoparticles loaded liposomes.

Treatment with doxorubicin (DOX) is a common treatment for different types of cancer. DOX-NP is one of a well established marketed liposomal formulation for DOX. It has advantages over free DOX in reducing the cardiac toxicity and increasing the efficacy. Gold nanoparticles (GNPs), have been widely used in biomedical applications such as medical imaging and biosensors. Mice bearing Ehrlich tumor were injected with saline, free doxorubicin (DOX) in solution, gold nanoparticles loaded liposomes and commercial liposomal encapsulated doxorubicin (DOX-NP). The results showed that GNPs loaded liposomes could enhance the antitumor activity of commercial liposomal formulation (DOX-NP) and displayed significantly decreased systemic toxicity compared with free DOX and commercial liposomal formulation (DOX-NP) at the equivalent dose. So the injection of GNPs and DOX-NP is expected to increase the cell killing and make it a promising approach to cancer treatment.

Ehrlich tumor inhibition using doxorubicin containing liposomes.

Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, DOX in solution or DOX encapsulated within liposomes prepared from DMPC/CHOL/DPPG/PEG-PE (100:100:60:4) in molar ratio. Cytotoxicity assay showed that the IC50 of liposomes containing DOX was greater than that DOX only. Tumor growth inhibition curves in terms of mean tumor size (cm(3)) were presented. All the DOX formulations were effective in preventing tumor growth compared to saline. Treatment with DOX loaded liposomes displayed a pronounced inhibition in tumor growth than treatment with DOX only. Histopathological examination of the entire tumor sections for the various groups revealed marked differences in cellular features accompanied by varying degrees in necrosis percentage ranging from 12% for saline treated mice to 70% for DOX loaded liposome treated mice. The proposed liposomal formulation can efficiently deliver the drug into the tumor cells by endocytosis (or passive diffusion) and lead to a high concentration of DOX in the tumor cells. The study showed that the formulation of liposomal doxorubicin improved the therapeutic index of DOX and had increased anti-tumor activity against Ehrlich tumor models.

Biophysical characterization of gold nanoparticles-loaded liposomes.

Gold nanoparticles were prepared and loaded into the bilayer of dipalmitoylphosphatidylcholine (DPPC) liposomes, named as gold-loaded liposomes. Biophysical characterization of gold-loaded liposomes was studied by transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy as well as turbidity and rheological measurements. FTIR measurements showed that gold nanoparticles made significant changes in the frequency of the CH(2) stretching bands, revealing that gold nanoparticles increased the number of gauche conformers and create a conformational change within the acyl chains of phospholipids. The transmission electron micrographs (TEM) revealed that gold nanoparticles were loaded in the liposomal bilayer. The zeta potential of DPPC liposomes had a more negative value after incorporating of Au NPs into liposomal membranes. Turbidity studies revealed that the loading of gold nanoparticles into DPPC liposomes results in shifting the temperature of the main phase transition to a lower value. The membrane fluidity of DPPC bilayer was increased by loading the gold nanoparticles as shown from rheological measurements. Knowledge gained in this study may open the door to pursuing liposomes as a viable strategy for Au NPs delivery in many diagnostic and therapeutic applications.

Liver uptake of gold nanoparticles after intraperitoneal administration in vivo: a fluorescence study.

BACKGROUND: One particularly exciting field of research involves the use of gold nanoparticles (GNPs) in the detection and treatment of cancer cells in the liver. The detection and treatment of cancer is an area in which the light absorption and emission characteristics of GNPs have become useful. Currently, there are no data available regarding the fluorescence spectra or in vivo accumulation of nanoparticles (NPs) in rat liver after repeated administration. In an attempt to characterise the potential toxicity or hazards of GNPs in therapeutic or diagnostic use, the present study measured fluorescence spectra, bioaccumulation and toxic effects of GNPs at 3 and 7 days following intraperitoneal administration of a 50 µl/day dose of 10, 20 or 50 nm GNPs in rats. METHODS: The experimental rats were divided into one normal group (Ng) and six experimental groups (G1A, G1B, G2A, G2B, G3A and G3B; G1: 20 nm; G2: 10 nm; G3: 50 nm; A: infusion of GNPs for 3 days; B: infusion of GNPs for 7 days). A 50 µl dose of GNPs (0.1% Au by volume) was administered to the animals via intraperitoneal injection, and fluorescence measurements were used to identify the toxicity and tissue distribution of GNPs in vivo. Seventy healthy male Wistar-Kyoto rats were exposed to GNPs, and tissue distribution and toxicity were evaluated after 3 or 7 days of repeated exposure. RESULTS: After administration of 10 and 20 nm GNPs into the experimental rats, two fluorescence peaks were observed at 438 nm and 487 nm in the digested liver tissue. The fluorescence intensity for 10 and 20 nm GNPs (both first and second peaks) increased with the infusion time of GNPs in test rats compared to normal rats. The position of the first peak was similar for G1A, G2A, G1B, G2B, G3B and the normal (438 nm); that for G3A was shifted to a longer wavelength (444 nm) compared to the normal. The position of the second peak was similar for G1A, G1B, G2A, G2B and the control (487 nm), while it was shifted to a shorter wavelength for G3A (483 nm) and G3B (483 nm). The fluorescence intensity of the first and second peaks increased for G1A, G2A, G1B and G2B, while it decreased for G3A and G3B compared to the control. CONCLUSIONS: The fluorescence intensity of GNPs varied with the number, size and shape of particles and with the ratio of surface area to volume in a given sample. Fluorescence intensity changes during infusion depended on the size and shape of GNPs, with smaller particles experiencing larger changes during the infusion time in addition to the quenching produced by the larger GNPs. It is likely that smaller particles, which have a much higher ratio of surface area to volume compared to larger particles, are more prone to aggregation and surface interaction with biological components. This study suggests that fluorescence intensity can be used to evaluate bioaccumulation and the toxicity of gold nanoparticles in rats.