Determination of the therapeutic efficacy of a novel Pheroid® formulation in a rodent tuberculosis model
Date
2019Author
Van der Merwe, Drieke
Venter, Kobus
Grobler, Anne
Cloete, Theunis
Lemmer, Yolandy
Metadata
Show full item recordAbstract
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
URI
http://hdl.handle.net/10394/33323https://www.sciencedirect.com/science/article/pii/S1056871919303260
https://doi.org/10.1016/j.vascn.2019.106608