Stigmurin encapsulated PLA–PEG ameliorates its therapeutic potential, antimicrobial and antiproliferative activities

Abstract

In light of growing global challenge posed by antimicrobial resistance, it is very important to explore alternatives that can target pathogenic microorganisms. One such strategy involves the use of antimicrobial peptides (AMPs) and Stigmurin is one such AMP present in Brazilian scorpion Tityus stigmurus which possesses antimicrobial, antiproliferative and antiparasitic activity. The study commenced with successful synthesis and characterization of Stigmurin and its analogues, designated S1 and S2. Studies on Stigmurin and its analogues have demonstrated that analogues exhibit enhanced antimicrobial efficacy but often lead to increased hemolysis, limiting their therapeutic application. To prevent the associated toxicity of these peptides, PLA–PEG di-block copolymer was synthesised to prepare nanoparticles (E-WT, E1, and E2) with an average diameter of approximately 160–180 nm. The core of the research involved evaluating the antimicrobial (Bacillus subtilis), antibiofilm (B. subtilis and Pseudomonas aeruginosa), antiproliferative (HEK293 and RAW264.7) and hemolytic activity of the peptides. In addition to the experimental work, in silico analysis using structural models was conducted to further understand their potential interactions. The findings demonstrated that the analogue peptides exhibit enhanced antimicrobial and antibiofilm activity compared to the wild-type Stigmurin. Moreover, encapsulating the peptides in PLA–PEG nanoparticles maintained the antimicrobial activity against B. subtilis. Further, encapsulation significantly reduced hemolysis as well as cytotoxicity by 10–20%, thereby improving their safety profile.

Graphical abstract