Forging a New Frontier: Antimicrobial Peptides and Nanotechnology Converging to Conquer Gastrointestinal Pathogens

Abstract

Gastrointestinal infections, which are caused primarily by pathogenic bacteria, remain a significant global health challenge. Their resilience is reinforced by various physical, biological, and biopharmaceutical barriers that complicate conventional therapeutic strategies. This review delves into the intricate landscape of managing these infections, addressing microbiota imbalances, the emergence of multidrug-resistant strains, and the impact of dysbiosis and antibiotic overuse. Faced with these challenges, traditional therapies often fail, which is hindered by low bioavailability, prolonged regimens, and a growing risk of resistance. In this context, nanotechnology applied to antimicrobial peptides (AMPs) has emerged as a promising solution to enhance their stability and targeted delivery. Through a critical approach, diverse nanocarriers and their efficacy against intestinal pathogens are evaluated both in vitro and in vivo. This review advocates for intensified research on the encapsulation and functionalization of AMPs, envisioning their potential to redefine the control of intestinal infections on a global scale.

Keywords: antimicrobial peptide; gastrointestinal infections; multidrug resistance; nanocarriers; nanoparticles.

Figure 1

Schematic representation of the main foodborne pathogens (E. coli, H. pylori, and Salmonella) affecting the human digestive system. The figure illustrates the ingestion of contaminated food, the specific colonization sites of each pathogen within the GIT (stomach and intestines), and a global map highlighting the regions with the highest disease burden and mortality associated with these infections.

Figure 2

Overview of the origin, biological functions, and current limitations of AMPs in the treatment of MDR bacteria. AMPs are derived from various natural sources, including mammals, insects, plants, fungi, and microorganisms. Their mechanisms of action include antibacterial and antibiofilm activities, modulation of the host immune response, and stimulation of epithelial cell proliferation. However, clinical application is limited by issues such as biological instability, cytotoxicity, and short half‐life.

Figure 3

In vitro evaluation of the release, inhibition, and stability of globulin peptide fractions and their SLN formulations after simulated gastrointestinal digestion. A) Release rates (%) of OGL and OGH from SLN at pH values of 1.2 and 6.5. B) DPP4 inhibition (%) over time for OGL, OGH, and their SLN formulations. C) Degree of hydrolysis (%) of OGL and OGH compared with their encapsulated versions. Reproduced with permission.^{[ 208 ]} Copyright 2020, Elsevier B.V.

Figure 4

AFM images obtained at a 7 µm² scan size of A) untreated P. aeruginosa biofilms; B) after treatment with 128 µg mL⁻¹ free (first row) and nanoencapsulated (second row) colistin sulfate at 6 h. C) Typical force‒distance curves of P. aeruginosa untreated (1) and treated with colistin (2) and the nanocarrier (3). Reproduced with permission.^{[ 218 ]} Copyright 2016, Elsevier B.V.

Figure 5

A) Effect of the applied formulations on PA01 (control strain), showing a significant reduction at all the tested tobramycin concentrations, while the MIC for free liposomes was 256 µg mL⁻¹. B) Effect of the formulations on MDR 7067 (resistant strain), where both free and formulated tobramycin had an MIC of 256 µg mL⁻¹, whereas empty liposomes showed no antibacterial activity. C,D) Biofilm formation in P. aeruginosa strains quantified by biomass measurements (OD 550 nm) after 48 h of exposure to free tobramycin and liposomal formulations: C) PA01 (control strain) and D) MDR 7067 (resistant strain). E) Viability of A549 cells after 48 h of exposure to different concentrations of empty liposomes, free tobramycin, tobramycin‐loaded liposomes, and tobramycin‐IDR‐1018‐loaded liposomes. Reproduced with permission.^{[ 226 ]} Copyright 2022, MDPI.

Figure 6

A) Micrographs of G17NP and B) G19NP obtained by scanning electron microscopy. (C) Antimicrobial activity of G19NP, G19, and NP against E. coli and D) MRSA. (■) G17NP, (□) G17, (▲) Empty nanoparticle, (●) G19NP, (○) G19. E) In vitro release profile of G17NP (▲) and G19NP (●) from polymeric nanoparticles under the same incubation conditions: 37 °C, pH 7.4, and 50 rpm. Reproduced with permission.^{[ 234 ]} Copyright 2020, MDPI.

Figure 7

A) AgNPs reduced by SF with an approximate size of 50 nm. B) AgNPs reduced by SF/AMP with a similar size. C) The ROS content in bacteria treated with Ag@AP/SF was greater than that in the other groups, indicating that the formation of AgNP@AMPs promotes ROS production, contributing to enhanced antibacterial activity. D) Cumulative release of Ag⁺ ions from the Ag@AP/SF system under different pH conditions. At pH 5 (red line), Ag⁺ is rapidly released, reaching ≈1.5 µg within the first few hours, whereas at pH 7.4 (green line), the release is slower and sustained, reaching only 0.15 µg over several days. E) Schematic representation of the system's behavior: under neutral conditions (green zone), Ag@AP/SF maintains controlled silver release, whereas in an acidic environment (red zone, simulating bacterial infection), the structure destabilizes, triggering accelerated Ag⁺ release due to silk fibroin transformation, thereby enhancing its pH‐activated antibacterial capability. Reproduced with permission.^{[ 249 ]} Copyright 2023, Elsevier B.V.