Search

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

Resistance against the current TB treatment regimens is spreading. A combination of the current TB regime with a novel drug delivery system, might lead to reduced resistance, shorter treatment durations and increased patient compliance. A delivery system is used to facilitate the delivery of specific therapeutically active ingredients to a targeted area in an organism (Vonarbourg et al., 2006). An ideal delivery system ought to be biodegradable, stable, pharmaceutically acceptable and suitable for targeted delivery (Buszello & Müller, 2000). The Pheroid® drug delivery system is such a system. It is an intricate polydisperse technology that is based on different colloidal emulsion systems (Grobler, 2009). In this study a novel Pheroid® drug delivery system was used with the addition of the mycobactericidal eicosapentaenoic fatty acid (EPA) and a targeting ligand Mycolic acid (MA). The in vivo anti-TB activity of the novel formulation alone, and in combination with the current treatment regime was determined against the H37Rv Mtb strain in the Kramnik mouse model. After inoculation, three groups of mice (n = 56) each received a different treatment formulation. Group 1 received the first line treatment API's (positive control), group 2 novel Pheroid® formulation and group 3 novel Pheroid® formulation in combination with the first line treatment API's. One group, group 4 (negative control), was infected but received no treatment. Six animals per treatment group were euthanised at different time intervals, i.e. at week 1, 2, 3, 4, 8 and lastly at week 12 and four animals in group 4 at different time intervals, i.e. at week 1, 8 and 12. Lungs were harvested for bacteriological examination in order to provide information regarding disease progression. Inflammation in the lungs indicates the presence of the Mtb infection, a direct correlation can be made between the mass of the lungs and the severity of the infection. Preliminary results obtained from the average mass of the lungs, showed that both group 1 and 3 suppressed the Mtb infection to a similar degree. Mice in these groups recovered quicker than those in groups 2 and 4. Some of the mice in group 2 and 4 reached the humane endpoint before the predetermined euthanasia dates, indicating an aggressive progression of the disease in these two groups. The preliminary results showed that the Mtb infection was suppressed in both treatment groups, group 1 and 3, while the carrier control (group 2) and the negative control (group 4) had no effect on the disease progression. Next the colony-forming units in the lung samples will be determined to give a more accurate quantitative measurement of the bacteriological infection. Further research will determine the relapse rate in the different study groups

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