Effect of emulsion-based nanosystems on the encapsulation behavior of triptorelin using molecular dynamics simulation.

The study explores the formulation of triptorelin, a therapeutic peptide used in prostate cancer treatment, within an emulsion-based delivery system to address challenges associated with rapid clearance and limited stability in aqueous environments. Molecular dynamics (MD) simulations were integrated with formulation design to provide molecular-level insight into the encapsulation process, interfacial organization, and hydration behavior of triptorelin in systems comprising palmitic acid, Tween 80, and polyethylene glycol 400 (PEG 400). Four distinct systems were analyzed: triptorelin–water, triptorelin–palmitic acid–water, triptorelin–palmitic acid–Tween 80–water, and triptorelin–palmitic acid–Tween 80–PEG 400–water. The MD results revealed a substantial reduction in water exposure for triptorelin within the excipient matrix, particularly in the fully developed system containing PEG 400. Palmitic acid promotes the encapsulation of hydrophobic regions of triptorelin within the emulsion droplet, while Tween 80 contributes to interfacial stabilization through interactions with lipid components. Notably, spontaneous droplet formation around the peptide was observed across all simulated systems, with the final formulation exhibiting enhanced structural stability. Collectively, the MD simulations establish a direct link between excipient composition and formulation performance, underscoring the synergistic roles of palmitic acid, Tween 80, and PEG 400 in generating a stable and well-defined emulsion-based delivery system. These findings demonstrate how MD simulations can be used as a rational method to design and optimize Triptorelin formulation strategies at the molecular level.