The effect of entrapment of a peptide in Pheroid® on pharmacokinetics and testosterone levels

Abstract

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