Morphology of nanostructures and their long-acting properties in vivo for a novel synthetic peptide of gonadotropin-releasing hormone antagonist.

Objectives To demonstrate the correlation between the nanostructure formation and the long duration of action in vivo of peptides, the morphology of nanostructures of LXT-101, a novel synthetic amphiphilic peptide of gonadotropin-releasing hormone antagonist were observed when dissolved in different solvents, and their long-acting properties in vivo were investigated in this study. Methods The morphology of nanostructures of LXT-101 was observed by transmission electron microscopy when dissolved in different solvents, and the plasma concentrations of LXT-101 and testosterone levels were also assayed for different solutions after intramuscular injection administration in beagle dogs. Key findings TEM data suggest that LXT-101 in pure water can form fibres, while in mannitol, dextrose or sodium chloride solution, they tend to form vesicles. The pharmacokinetic and pharmacodynamic results showed that the plasma concentrations of LXT-101 within 48 h were much higher but descended dramatically with mannitol, dextrose and NaCl solutions structurally composed of vesicles compared with that of pure water structurally composed of fibres. An effectively suppression of testosterone can be achieved only 2 or 3 days with the frontal three solutions, while LXT-101 in pure water maintained over a period of 7 days. Conclusions It may indicate that LXT-101 peptide in pure water forms fibre depot that release monomeric active peptide slowly. The correlation between the nanostructure and duration of action in vivo suggests that the addition of excipients influence self-assembly process of LXT-101 that leads to the formation of different nanostructures and exhibit various behaviours in vivo.