Dexmedetomidine has been widely used clinically for perioperative sedation and analgesia, accompanied by the shortcomings of cardiovascular adverse effects and short duration. Although developing a slow-releasing dexmedetomidine formulation is a conventional strategy to address these problems, it is unfortunately limited by the small molecule and high solubility of the drug. In this study, we designed a self-assembling peptide (SAP) by referring to the chemical structure of dexmedetomidine, which contains a pH-responsive imidazole group and a hydrophobic benzene group. By also containing the two groups, the peptide could simultaneously undergo pH-induced phase-transition together with dexmedetomidine, leading to their co-assembly to form drug-peptide complexes. Different from well-ordered nanofibers formed by the peptide alone, the co-assembly system formed nanoparticles with relatively disordered core structures like biomolecular condensates. In this manner, the obtained formulation exhibited high drug encapsulation efficiency and a slow-releasing profile, which further alleviated hypotension and extended the duration of sedative and analgesic efficacy in animal models. This study proposed a promising strategy to design SAPs for drug delivery in a personalized way. It also provided the slow-releasing dexmedetomidine formulation as a promising candidate for clinical application.
Xie et al. (Fri,) studied this question.