Self-Assembly Nanostructure of Myristoylated ω-Conotoxin MVIIA Increases the Duration of Efficacy and Reduces Side Effects

• Published in: Marine drugs 2023-04, Vol.21 (4), p.229
• Main Authors: Ding, Xiufang, Wang, Yue, Zhang, Sida, Zhang, Ruihua, Chen, Dong, Chen, Long, Zhang, Yu, Luo, Shi-Zhong, Xu, Jianfu, Pei, Chengxin
• Format: Article
• Language: English
• Subjects: analgesia; Analgesics; Animals; Bioavailability; Calcium Channel Blockers - pharmacology; Calcium channels; Calcium channels (N-type); Calcium channels (voltage-gated); Calcium ions; Chemical properties; Chronic illnesses; Chronic pain; Chronic Pain - drug therapy; Complications and side effects; conotoxin; Dosage and administration; Drug delivery systems; Drug dosages; Drug therapy; Drugs; Duration; Fatty acids; Health aspects; Health problems; Insulin; Marine toxins; Mice; Micelles; Molecular chains; myristoylation; Nanoparticles; omega-Conotoxins - pharmacology; Pain; Particle size; Peptides; Peptides - pharmacology; Pharmaceutical research; Physiology; Self-assembly; Side effects; Structure; Toxins; Tremor; Vehicles; Ziconotide
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md21040229

Chronic pain is one of the most prevalent health problems worldwide. An alternative to suppress or alleviate chronic pain is the use of peptide drugs that block N-type Ca channels (Ca 2.2), such as ω-conotoxin MVIIA. Nevertheless, the narrow therapeutic window, severe neurological side effects and low stability associated with peptide MVIIA have restricted its widespread use. Fortunately, self-assembly endows the peptide with high stability and multiple functions, which can effectively control its release to prolong its duration of action. Inspired by this, MVIIA was modified with appropriate fatty acid chains to render it amphiphilic and easier to self-assemble. In this paper, an N-terminal myristoylated MVIIA (Myr-MVIIA, medium carbon chain length) was designed and prepared to undergo self-assembly. The present results indicated that Myr-MVIIA can self-assemble into micelles. Self-assembled micelles formed by Myr-MVIIA at higher concentrations than MVIIA can prolong the duration of the analgesic effect and significantly reduce or even eliminate the side effects of tremor and coordinated motor dysfunction in mice.