Reverse micelle-lipid nanocapsules: a novel strategy for drug delivery of the plectasin derivate AP138 antimicrobial peptide

Abstract

IntroductionResistance to traditional antibiotics is an increasingly serious problem. Antimicrobial peptides (AMPs) have emerged as a new therapeutic class with great potential against infectious diseases, as they are less prone to induce resistance. Nanotechnology-based delivery strategies can improve the efficiency and stability of AMPs, particularly against proteolytic degradation. Lipid nanocapsules (LNCs) are a new generation of biomimetic nanocarriers and were used in this study to deliver peptides.MethodsAMP-loaded reverse micelles (RM) were developed and incorpo rated into LNCs by the phase inversion process and the antimicrobial activity of the AMPs-loaded LNC was evaluated by the minimum inhibitory concentration method. We studied the activity of AMP solutions and AMP-loaded LNCs against Gram-positive and Gram-negative bacterial strains and then evaluated the encapsulation of a new cationic AMP called AP138. Finally, we analyzed the effect of enzymatic attack on AP138 and AP138-RM-LNCs after incubation with trypsin.ResultsAP138 was efficiently encapsulated in the LNCs (encapsulation efficiency = 97.8% at a drug loading of 0.151%), resulting in protection against degradation by proteases and the preservation of antimicrobial activity against Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus.ConclusionThis study shows that RM-LNCs are an excellent candidate system to deliver AMPs.

Versatility of Reverse Micelles: From Biomimetic Models to Nano (Bio)Sensor Design

“…have been proposed. Many well-documented reviews and comprehensive books have been published during the years of study, including the latest ones approaching the assessment of current knowledge and dealing with several aspects of reverse micelles [7][8][9][10][11][12][13].…”

Antimicrobial peptides as therapeutic agents: opportunities and challenges

“…Another main strategy to improve the half-life and performance of AMPs is to use advanced delivery vehicles. Interestingly, the use of nanoparticles for the delivery for AMPs has recently been intensely explored, since nanocarriers provide a large surface area for adsorption/encapsulation of AMPs and also enable to prevent peptide self-aggregation [106][107][108][109][110][111][112][113]. In the opinion of the authors, these efforts are most promising with regard to the local delivery of AMPs, whereas meaningful improvements allowing peroral and systemic delivery still remain challenging.…”

Incorporation of Antibiotics into Solid Lipid Nanoparticles: A Promising Approach to Reduce Antibiotic Resistance Emergence

“…Although several publications demonstrate the capability of different organic nanoparticles to protect antibiotics from bacterial enzyme degradation (e.g., polymeric nanoparticles [ 93 ], liposomes [ 94 ] and micelle–lipid nanocapsules [ 93 , 94 , 95 ]), there is no publication, at least in our knowledge, related to the protection against enzymatic activity presented by SLNs.…”