Enhanced Antibacterial Activity of Dermaseptin through Its Immobilization on Alginate Nanoparticles—Effects of Menthol and Lactic Acid on Its Potentialization

Abstract

Dermaseptin B2 (DRS-B2) is an antimicrobial peptide secreted by Phyllomedusa bicolor, which is an Amazonian tree frog. Here, we show that the adsorption of DRS-B2 on alginate nanoparticles (Alg NPs) results in a formulation (Alg NPs + DRS-B2) with a remarkable antibacterial activity against Escherichia coli ATCC 8739 and E. coli 184 strains, which are sensitive and resistant, respectively, to colistin. The antibacterial activity, obtained with this new formulation, is higher than that obtained with DRS-B2 alone. Of note, the addition of lactic acid or menthol to this new formulation augments its antibacterial activity against the aforementioned Gram-negative bacilli. The safety of DRS-B2, and also that of the new formulation supplemented or not with a small molecule such as lactic acid or menthol has been proven on the human erythrocytes and the eukaryotic cell line types HT29 (human) and IPEC-1 (animal). Similarly, their stability was determined under the conditions mimicking the gastrointestinal tract with different conditions: pH, temperature, and the presence of digestive enzymes. Based on all the obtained data, we assume that these new formulations are promising and could be suggested, after in vivo approval and completing regulation aspects, as alternatives to antibiotics to fight infections caused by Gram-negative bacilli such as E. coli.

Evaluation of the Antibacterial Activity of New Dermaseptin Derivatives against Acinetobacter baumannii

“…Combining DRS-B2 with alginate nanoparticles (Alg NPs) results in a formulation (Alg NPs + DRS-B2) that creates novel B2 derivatives displaying significant antibacterial efficiency against both susceptible and resistant strains of Escherichia coli to colistin. The antibacterial activity achieved with this innovative formulation exceeds that of DRS-B2 when used alone [ 26 ]. Moreover, our synthesized peptides offer the advantage of being configured with D-amino acids.…”

“…Sruthy et al [ 57 ] confirmed that at the highest tested concentration of histone H2A-derived antimicrobial peptide (200 μM), growth inhibition of 89% was observed in HEp2 cell lines. Another study conducted by Hazime et al [ 26 ] tested the cytotoxic effects of DRS-B2 and of a new formulation (Alg NPs + DRS-B2) on the human erythrocytes and eukaryotic cell line types HT29 (human) and IPEC-1 (animal); in that study, their safety was verified. Zairi et al [ 58 ] found that dermaseptin K 4 S4 exhibited an enhanced toxicity profile against human endometrial epithelial cells, displaying lower sensitivity to the toxic effects of dermaseptins compared to other cell types.…”

“…Belaid et al [55] demonstrated that the maximal non-cytotoxic concentrations were 32 µg/mL for DRS-S1 and DRS-S2, 16 µg/mL for DRS-S3 and DRS-S4, and 64 µg/mL for dermaseptin S5 to HEp-2 cells. Additionally, the study of Gourkhede et al [56] indicated that other AMPs, like Cecropin A (1-7)-Melittin and lactoferricin (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), exhibited negligible cytotoxicity at lower concentrations (1X and 2X MIC); however, at 4X MIC, slightly higher cytotoxicity was observed, given that the MIC values were equal to 64 µg/mL and 128 µg/mL, respectively. Sruthy et al [57] confirmed that at the highest tested concentration of histone H2A-derived antimicrobial peptide (200 µM), growth inhibition of 89% was observed in HEp2 cell lines.…”

“…Among the peptides of the DRS family, DRS-B2 stands out, with the highest level of activity, making it the subject of extensive research. This amphipathic (+3) cationic polypeptide is composed of 33 amino acids, with a molecular weight of approximately 3180 Da, a tryptophan residue at position 3, and six lysine residues [ 26 ]. This α-helical peptide has the ability to disrupt the membranes of a wide range of microorganisms, such as bacteria, yeast, fungi, and protozoa.…”

Nanoparticle formulations for therapeutic delivery, pathogen imaging and theranostic applications in bacterial infections

“…Due to their biocompatibility and biodegradability, natural polymers, including chitosan, alginate, and albumin, have been investigated as drug carriers [88][89][90][91][92][93][94][95][96][97]. For example, ceftriaxone-loaded chitosan tripolyphosphate nanoparticles exhibited enhanced antibacterial effects against intracellular S. typhimurium (Salmonella typhimurium) than the inefficient free drug [98].…”