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To evaluate the efficacy of newly synthesized therapies prior to clinical trials, valid and true cancer models should be used [1]. For modelling cancer in vivo, transplantation of rodent (allograft) and human cancer cells (xenograft) in immune-competent and immunedeficient mice, respectively is common [2]. The aim of this study was to develop and characterize breast cancer allograft and human ovarian xenograft cancer rodent models. The allograft model was established by injection of E0771 cells suspended in Matrigel, subcutaneously into the mammary fat pad of female C57BL/6 mice. For xenograft model, human OVCAR-3 cells suspended in Matrigel were injected subcutaneously into the hind flank of athymic nude female mice. Once a tumor was palpable, tumor growth was monitored 2–3 times a week using a digital caliper and the animals were euthanized once tumor volume of ≥300 mm3 was attained. Finally, haematoxylin and eosin staining of the tumors was conducted to confirm malignancy. For the E0771 derived allograft model (Fig. 1), tumors were detectable within a week post inoculation with a tumor take rate of 14/14 (100%). For OVCAR-3 derived xenograft model (Figure1B), tumors were detected approximately 5 weeks post inoculation with tumor take rate of 3/4 (75%). Histological analysis of both models revealed mitotic figures indicating that the tumors were actively proliferating and malignant. The rodent models of breast and ovarian cancer were successfully established and characterized and; can be used to evaluate novel clinical compounds and formulations

The Pheroid® technology is a patented colloidal drug delivery system comprised of a dispersed oil phase of omega 3 and omega 6 fatty acids emulsified in N2O saturated water. Pheroid® has pharmaceutical applicability for the enhancement of therapeutic efficacy due to better drug exposure, reduced cytotoxicity and faster onset of action. The purpose of this paper was to evaluate the possible cardiovascular effects of the Pheroid® drug delivery system in the conscious rat. Six male rats instrumented with telemetry transmitters were used in a three-way crossover design. The effects of single intravenous administrations of Pheroid® and oral administration of Pheroid® and pro-Pheroid® on cardiovascular parameters were measured. These parameters included arterial blood pressure, heart rate and the ECG. As positive controls, a single intraperitoneal dose of clonidine (0.03 mg/kg) and an oral dose of theophylline (30 mg/kg) were also tested. No significant effects of Pheroid® on cardiovascular parameters were observed at any time following oral or intravenous administration. The expected effects of clonidine (decreased heart rate) and theophylline (increased heart rate) could be demonstrating confirming the sensitivity of the experimental model to detect changes in the cardiovascular parameters measured. We have demonstrated that Pheroid® has no effects on cardiovascular function following both oral and intravenous administration. These data showing cardiovascular safety are supportive for the use of Pheroid® for various pharmacological applications

Goserelin is a peptide drug that suppresses levels of testosterone and oestradiol [1]. The current formulation is presented in a sustained-release depot with several approved indications such as treatment of endometriosis, prostate cancer and breast cancer. The depots are placed subcutaneously with a large bore needle, hence there is a need for less invasive administration. An oral formulation in a drug delivery system such as Pheroid® would offer ease of administration to the patient, improved bioavailability as well as reduced manufacturing costs [2]. Therefore, the aim of this study was to determine the effect of entrapment of goserelin in Pheroid® on the pharmacokinetics (PK) of goserelin as well as the pharmacodynamic (PD) effects, in mice. Goserelin was entrapped in Pheroid® and characte- rized in terms of size, zeta potential and morphology. Male Balb/c mice, 6–8 weeks old were administered goserelin subcutaneously and goserelin entrapped in Pheroid® orally. At selected time points, mice were euthanised, blood collected and analysed for goserelin and testosterone levels by LCMS/MS to determine the PK and PD effects respectively. The size and zeta potential of Pheroid® remained in the expected ranges suggesting that entrapment of goserelin had no effect on Pheroid® vesicle size and stability. Confocal imaging showed satisfactory quality of the Pheroid® and goserelin did not have any effect on the Pheroid® structure. Entrapment of goserelin in Pheroid led to detectable levels of goserelin in plasma of the mice and a corresponding decrease in testosterone levels. The results suggest that Pheroid® may improve the oral bioavailability of goserelin and could be a potential strategy for an oral formulation which would be less invasive for patients

Goserelin is a type of hormone therapy used in addition to standard adjuvant therapy. Currently, goserelin is only available as a slow releasing subcutaneous implant but this is an invasive and generally not well- tolerated method of administration. By using a drug delivery system (DDS), peptides can be protected from the harsh environment of the gastrointestinal (GI) tract. Pheroid® technology is one such example of a drug delivery system. This delivery system is a patented, colloidal drug delivery system and is capable of targeting specific areas for treatment, transportation of genetic material to the cellular nucleus and the decrease of drug resistance, all this while improving the delivery of dynamic complexes [1,2]. The prospect of changing to a less invasive administration method will yield a great advantage. Goserelin was investigated in female Balb/c mice. Pheroid® technology was used as a drug delivery system (DDS) to compare the bioavailability of goserelin subcutaneous depot against a peroral formulation with goserelin pro-Pheroid® formulation. The mice were divided into three groups; group one received goserelin subcutaneously, group 2 received an oral dose of 4 mg/kg pro-Pheroid®-goserelin and group 3 being the control group which received only pro- Pheroid®. Vaginal cytology was evaluated to track the disruption of the oestrus cycle Vaginal cytology results indicated a disruption in the oestrus cycle in the subcutaneous groups and the pro- Pheroid®-goserelin oral group. No disruption in the cycle was observed for the pro-Pheroid® oral group. Entrapment in Pheroid® resulted in oral bioavailability of goserelin as indicated by the related effect on the oestrus cycle. No disruption of the cycle was observed in the pro-pheroid® oral group, thus, goserelin was successfully absorbed in the blood after the peroral administration with pro-Pheroid. In conclusion, Pheroid® technology seemed to protect goserelin from the harsh environment of the gastrointestinal tract and could thus be a helpful DDS

Colloidal suspensions of 14 nm gold nanoparticles (AuNPs) were repeatedly administered intravenously at three dose levels (0.9, 9 and 90 µg) to male Sprague Dawley rats weekly for 7 weeks, followed by a 14-day washout period. After sacrificing, the amount of gold was quantified in the liver, lungs, spleen, skeleton and carcass using neutron activation analysis (NAA). During the study, pre- and post (24 h) administration blood samples were collected from both the test and control groups, the latter which received an equal injection volume of normal saline. General health indicators were monitored together with markers of kidney and liver damage for acute and subchronic toxicity assessment. Histopathological assessments were done on the heart, kidneys, liver, lungs and spleen to assess any morphological changes as a result of the exposure to AuNPs. The mass measurements of all the groups showed a steady increase with no signs of overt toxicity. The liver had the highest amount of gold (µg) per gram of tissue after 56 days followed by the spleen, lungs, skeleton and carcass. Markers of kidney and liver damage showed similar trends between the pre and post samples within each group and across groups. The histopathological examination also showed no hepatotoxicity and nephrotoxicity. There was accumulation of Au in tissues after repeated dosing, albeit with no observable overt toxicity, kidney or liver damage.

Dinuclearbisphosphinogold(I) dithiocarbamato, BPDTC, was previously found to have antitumour activity in vitro. 198Au radiolabelled BPDTC (radiochemical yield of 70 ± 6 % and radiochemical purity of[95 %) was used to determine its in vivo biodistribution in Sprague-Dawley rats. Gamma scintigraphs were performed over a period of 48 h and final radioactivity measurements of harvested organs of the test animals after termination was performed at 2, 4 and 48 h. The study successfully showed the biodistribution of the gold complex, with the highest uptake of the compound being observed in the lungs, liver and spleen Nuclear Technologies in Medicine and the Biosciences Initiative (NTeMBI), a national technology platform developed and managed by the South African Nuclear Energy Corporation (Necsa) and funded by the Department of Science and Technology. Biomed (Mintek)

The biodistribution of an N2N2 0 tetradentate gold(III) chelate, which is known to be cytotoxic towards a range of human cancer cell lines, was determined by a radiolabelled equivalent of the compound. The 198Au-labelled gold(III) chelate of a bis(pyrrolide-imine) Schiff base ligand with a three-carbon di(azomethine) linkage was successfully synthesised with a high radiochemical yield of 73% and radiochemical purity of >95%. The high energy g-ray emitted by the 198Au nucleus was used to follow the biodistribution of the compound in vivo in six male Sprague Dawley rats on a gamma camera. The log Po/w value of the natAu analogue, 1.92(2), showed that the compound is hydrophilic and therefore likely to largely remain in the blood pool. This was confirmed by the biodistribution study, which showed 21% of the injected dose (ID) remained in the blood pool 4.5 h after injection. This decreased to 10.8% over a 24-h period. The activity measured in the lungs, 1.48%ID/g, remained relatively constant over a 24-h period suggesting that the complex had accumulated in the lungs in the form of particulates, and could not be cleared by the test subjects. The t½ for the heart and lungs was greater than 24 h. Excretion of the test compound is seemingly via the kidneys, but is slow with approximately 30% of the ID excreted within 24 h. http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%291099-1344