pH-sensitive polyion nanocomplexes for antimicrobial peptide delivery

As an alternative to antibiotics, antimicrobial peptides (AMPs) are attracting more and more attention for non-antibiotic antibacterial therapy. However, there are still many issues of AMPs for clinical applications. For example, AMPs are generally positively charged and can be easily cleared during blood circulation. In addition, the cationic AMPs show strong cytotoxicity, which brings potential biosafety risks. In order to address these issues, pH-sensitive polyion nanocomplex is designed for the delivery of AMPs by electrostatic self-assembly of positively charged AMPs Magainin-I and negatively charged 2,3-dimethyl maleic anhydride (DA) modified ε-polylysine (EPL) (EPL-DA). The size and surface charge of the polyion nanocomplex is fully investigated by dynamic laser scattering (DLS) and transmission electron microscope (TEM). Magainin-I loaded polyion nanocomplex is stable in physiological environment (pH 7.4), which can effectively reduce the cytotoxicity of AMPs. In the slightly acidic environment (pH 5.0–6.0) in bacteria infected tissue, the nanocomplex would be disintegrated to positively charged EPL and Magainin-I, thereby restoring antibacterial properties. The excellent antibacterial activity of Magainin-I loaded polyion nanocomplexes is confirmed by a series of in vitro antibacterial experiments. The fabrication of polyion nanocomplex provides an innovative way for the delivery of AMPs.     

Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues

Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes’ pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an acne vulgaris model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (Pseudomonas stutzeri, Enterococcus faecium and Bacillus thuringiensis). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-β/collagen, Wnt/β-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.