Oral delivery of oil-based formulation for a novel synthetic cationic peptide of GnRH (gonadotropin-releasing hormone) antagonist for prostate cancer treatment

LXT-101, a cationic peptide is a novel antagonist of gonadotropin-releasing hormone (GnRH) for prostate cancer treatment. However, effective delivery of peptide drugs into the body by the oral route remains a major challenge due to their origin properties with high molecular weights, strong polarity and low stability in the gastrointestinal (GI) tract. In this study, we have developed a novel oral delivery of oil-based formulation in which therapeutic peptide LXT-101 are solubilized in oils and with this solution as oil phase, an optimum formulation of self-microemulsifying drug delivery system (SMEDDS) was developed. The peptide stability with the SMEDDS formulation in artificial gastric and intestinal fluid was tested in vitro. On the other hand, the testosterone level and plasma concentration of LXT-101 in rats after oral administration of the SMEDDS formulation were investigated in vivo. The data in vitro indicated that LXT-101 in the SMEDDS formulation was stable over 8 h in artificial gastric and intestinal fluid. LXT-101 can be absorbed in vivo and suppression of testosterone maintained in castration level within 12 h can be achieved effectively after SMEDDS formulation administered orally at a dose of 3.5 mg/kg. The approach can provide a potential way for delivery peptides by oral.

(A) Stability of LXT-101 aqueous solution and oral formulation (SMEDDS) containing LXT-101 in artificial intestinal fluid (mean ± S.D., n = 2). (B) Plasma concentration–time curve of testosterone in rats with dose of 3.5 mg/kg (mean ± S.D., n = 5).Figure optionsDownload high-quality image (113 K)Download as PowerPoint slide