Determination of the therapeutic efficacy of a novel Pheroid® formulation in a rodent tuberculosis model

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