The effect of entrapment of a peptide in Pheroid® on pharmacokinetics and testosterone levels
Date
2019Author
Hayeshi, Rose
Erasmus, Linné
Scholtz, Liezl-Marie
Venter, Kobus
Bester, Cor
Fick, Antoinette
Leussa, Nyango-Nkeh Adrienne
Grobler, Anne
Metadata
Show full item recordAbstract
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
URI
http://hdl.handle.net/10394/33315https://www.sciencedirect.com/science/article/pii/S1056871919303260
https://doi.org/10.1016/j.vascn.2019.106608